肝脏去唾液酸糖蛋白受体的生物学特性研究及其特异性适配子的筛选与鉴定
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摘要
目的
1.研究肝脏去唾液酸糖蛋白受体(asialoglycoprotein receptor,ASGPR)大亚基异构体的产生机制、表达水平及其编码蛋白的特性,为进一步阐明ASGPR的生物学功能及以其为靶标的肝脏靶向治疗奠定基础。
2.筛选获得能够特异性高亲和力结合肝脏特异性去唾液酸糖蛋白受体的RNA适配子,为开发诊断和治疗肝脏疾病的靶向性试剂和药物奠定基础。
方法
1.从正常人肝组织和HepG2细胞中克隆ASGPR大亚基H1的两种异构体H1a和H1b的cDNA序列,测序并比对分析H1b的产生机制;实时荧光定量PCR检测正常人肝组织和HepG2细胞中H1a和H1b的表达比例,以及在HBV、HCV感染情况下和肝癌组织中H1b表达水平的变化.
2.合成H1b特异性多肽并与钥孔戚血蓝素(KLH)偶联,免疫小鼠制备H1b特异性多克隆抗体,鉴定抗体的效价和特异性;亲和柱层析的方法从人血清和HepG2细胞培养上清中分离并纯化可溶性ASGPR,采用特异性抗体通过Western blot鉴定可溶性ASGPR的组成;免疫组织化学检测H1b在肝组织中表达和定位。
3.合成一个长度为115nt含有25个随机序列的单链DNA随机文库,通过体外转录构建出单链RNA适配子随机文库,从肝组织中分离纯化ASGPR大亚基作为靶蛋白,采用SELEX(systematic evolution of ligands by exponential enrichment)技术筛选高亲和力的ASGPR特异性RNA适配子;测序分析筛选适配子的序列,预测并分析其二级结构特点。
4.同位素~(32)p标记适配子,通过膜结合测定实验、凝胶阻滞实验鉴定筛选适配子对靶蛋白的特异性和亲和力;绿色荧光FITC标记适配子,鉴定其与肝细胞系HepG2和Huh7的特异性结合。
结果
1.人肝组织和肝细胞系HepG2中普遍表达ASGPR大亚基异构体H1a和H1b,H1b的cDNA较H1a缺失了一段117 nt的序列,该序列是ASGPR大亚基编码基因的第二个外显子,其两端具有典型的AG/GT序列,提示H1的两种异构体产生于对ASGPR mRNA的选择性剪接。
2.正常肝组织和HepG2细胞中H1a和H1b的表达比例分别为5.2:1和2.6:1,而且H1b的表达水平在HBV和HCV感染细胞中下降约60%,在肝癌组织中下降90%以上。
3.在从正常人血清和HepG2细胞培养上清中纯化的可溶性ASGPR蛋白中,可以检测到H1b蛋白单体以及H1b和H2构成的多聚体;对肝组织进行的免疫组织化学检测显示H1b不能定位至细胞膜,而主要存在于细胞质中。
4.经过12轮SELEX筛选,适配子文库中与靶蛋白结合的适配子得到明显富集;对第12轮文库中随机挑选的48个适配子进行测序并预测其二级结构,发现文库中适配子从结构上主要由两个家族构成,其占总适配子的比例分别为45.8%和33.3%;并找到一个适配子H1-A25与靶蛋白具有很高的亲和力,Kd值为48.79nM。
5、在膜结合测定实验和凝胶阻滞实验中,反应体系中不添加靶蛋白,或用无关蛋白替代靶蛋白,则不能检测到明显的适配子H1-A25和蛋白结合;而在反应体系中加入过量未标记适配子H1-A25,则能明显阻断放射标记适配子H1-A25与H1蛋白的结合。
6、FITC标记的适配子H1-A25能结合至肝癌细胞系HepG2和HuH-7,但不能结合不表达ASGPR的HeLa细胞;加入ASGPR的多克隆抗体可部分阻断荧光标记适配子H1-A25与HepG2细胞或HuH-7细胞结合,而加入过量未标记适配子H1-A25则几乎可以完全阻断荧光标记适配子H1-A25结合HepG2细胞的荧光信号。
结论
1.人肝组织及肝细胞系HepG2和Huh7中普遍表达ASGPR大亚基异构体H1a和H1b。
2.大亚基异构体H1b编码的蛋白为分泌型H1。
3.血清中的可溶性ASGPR是由分泌型的H1和H2构成的功能性复合物。
4.成功地筛选出了具有高亲和力的肝脏ASGPR特异性RNA适配子H1-A25。
5.适配子H1-A25能特异性靶向结合至肝细胞。
本研究的创新点及意义
1.首次发现人类肝脏去唾液酸糖蛋白受体大亚基H1存在剪接异构体H1b,并证明此剪接异构体编码的分泌型蛋白参与构成功能性的可溶性ASGPR,从而完善了对可溶性ASGPR的认识,并为进一步全面系统探讨ASGPR的生物学功能奠定了坚实的基础。
2.本研究首次筛选得到了肝细胞特异性的RNA适配子并鉴定了其功能,而对其进一步的改进和修饰将使其有望成为新的诊断和治疗肝脏疾病的靶向性试剂和药物载体。
Objective
1. To study the occurrence mechanism, expression level and protein characteristics of the major subunit variants of human asialoglycoprotein receptor, and lay a foundation for further study of the function of ASGPR and for hepatic targeting therapy through ASGPR.
2. To obtain RNA aptamer with high affinity and specificity to the human liver specific asialoglycoprotein receptor (ASGPR) and lay a foundation for developing new reagents or drugs for the diagnosis and the targeting treatment of liver diseases.
Methods
1. Two major subunit variants of ASGPR (H1a and H1b) were cloned from normal human liver tissues and HepG2 cells, the occurrence mechanism of variant H1b was analyzed by sequences comparison. The expression levels of H1a and H1b in normal liver tissues and HepG2 cells were determined by real-time fluorescence quantitative PCR, as well as the level changes in HBV or HCV infected cells and HCC tissues.
2. H1b specific peptide was synthesized and coupled with keyhole limpet hemocyanin (KLH) for immunization. Then H1b-KLH conjugation was injected into mouse subcutaneously to produce polyclonal antibody. The titer and specificity of the antibody were confirmed. Soluble ASGPR (sASGPR) in normal human sera or HepG2 cell supernatants were purified by lactose-agarose affinity chromatography, and the compositions of sASGPR were analyed by specific antibodies. The expression and location of protein H1b in liver tissues were also determined by immunohistochemistry.
3. A single-stranded 115 nucleotides (nt) random DNA library containing 25 random oligonucleotides was synthesized in vitro, then random RNA aptamers library was constructed by in vitro transcription. Aptamers that can specifically bind to human hepatic asialoglycoprotein receptor was isolated from the RNA random library by using the SELEX (systematic evolution of ligands by exponential enrichment) procedure. Selected aptamers were analyzed by sequencing, and the secondary structures of these aptamers were prediced and analyzed by using RNA Structure Program.
4. Aptamers were labeled by ~(32)P, then filter biding assay and gel shift assay were performed to determine the specificity and affinity of the selected aptamers. One apatamer was also labeled by FITC, and the binding between the aptamer and the human hepatoma cell lines HepG2 and HuH-7 were identified by fluorescent staining.
Results
1. Two variants of ASGPR H1, designated H1a and H1b, are extensively expressed in both human liver tissues and in human hepatoma cell lines HepG2 and Huh7. Cloning of ASGPR H1 splice variant cDNAs and subsequent sequence analysis revealed that they differ only in the presence of 117 nt. This 117 nt segment corresponds to exon 2 in the genomic sequence of ASGPR, and the typical AG/GT 5' consensus splice donor and acceptor sites were found at each end of the 117 nt segment, strongly suggesting that ASGPR H1b is generated by alternative splicing of ASGPR mRNA.
2. The ratio of ASGPR H1a to H1b was about 2.6:1 in normal human liver tissue and 5.2:1 in HepG2 cells. H1b expression were decreased by approximately 60% in HBV or HCV infected cells, and were decreased more than 90% in HCC tissues.
3. Both the H1b protein and a functional soluble ASGPR (sASGPR) composed of H1b and H2 were identified in both normal human sera and in the supernatant of HepG2 cells. Immunohistochemistry analysis shows that protein H1b in liver tissues can not accumulate at the cellular membrane, but in the cytoplasm.
4. Twelve rounds of selection and amplification were performed, and the aptamers which can bind to H1 were significantly enriched. Round 12 RNAs were amplified by RT-PCR and cloned. Forty-eight randomly picked plasmid clones were sequenced. The secondary structures of these aptamers were predicted with RNA Structure Program. Most aptamers of Round 12 RNAs were represented by only two kinds of structures, and their percentages of composition of Round 12 RNAs were 45.8% and 33.3%, respectively. One aptamer, H1-A25, was found to have high affinity to protein H1. the dissociation constant for the aptamer:H1 complex was estimated to be 48.79 nM.
5. While P~(32)-labeled H1-A25 significantly bound to H1 protein on the nitrocellulose filter (determined by nitrocellulose filter binding assay), its binding to HBsAg, the HBV S antigen that served as a negative control, was similar to that of probe alone. Furthermore, gel mobility shift assays also confirmed the specific binding of aptamer H1-A25 to H1 protein, as only recombinant H1 but not HBsAg, could cause the retardation of mobility of P~(32)-labeled H1-A25 probe. The addition of 100-fold excess unlabeled aptamer to the reaction system abolished the aptamer-H1 interaction.
6. FITC labeling H1-A25 specifically bound to the ASGPR-expressing hepatoma cell lines HepG2 and Huh-7. However, no binding was shown to the ASGPR-negative cell line HeLa. The fluorescence signal was significantly reduced by preincubating HepG2 cells with anti-H1 polyclonal antibody and can be nearly blocked by adding 100-fold excess unlabeled H1-A25.
Conclusions
1. Two variants of ASGPR H1, designated H1a and H1b, are extensively expressed in both human liver tissues and in human hepatoma cell lines HepG2 and Huh7.
2. The protein encoded by the H1b variant is a secreted form of H1.
3. sASGPR is a hetero-oligomeric complex of the secreted form of H1 and H2 and is able to bind a lactose-agarose substrate.
4. RNA aptamer H1-A25 that can specifically bind to human hepatic ASGPR with high affinity was successfully selected by using SELEX.
5. Aptamer H1-A25 can specifically bind to human hapatocytes.
Significances of the study
1. Our works provide the first evidence of the existence of splice variant H1b of human hepatic ASGPR H1, and prove that the protein encoded by the variant H1b is a secreted form of H1 which participates in the composing of sASGPR complex. The study improved the understanding of sASGPR, and laid a foundation for further comprehensive study of the function of ASGPR.
2. This is the first reported RNA aptamer which could bind to a human hepatic specific receptor. And this newly isolated aptamer could be modified to deliver imaging, diagnostic, and therapeutic agents targeted at hepatic parenchymal cells.
1.研究肝脏去唾液酸糖蛋白受体(asialoglycoprotein receptor,ASGPR)大亚基异构体的产生机制、表达水平及其编码蛋白的特性,为进一步阐明ASGPR的生物学功能及以其为靶标的肝脏靶向治疗奠定基础。
2.筛选获得能够特异性高亲和力结合肝脏特异性去唾液酸糖蛋白受体的RNA适配子,为开发诊断和治疗肝脏疾病的靶向性试剂和药物奠定基础。
方法
1.从正常人肝组织和HepG2细胞中克隆ASGPR大亚基H1的两种异构体H1a和H1b的cDNA序列,测序并比对分析H1b的产生机制;实时荧光定量PCR检测正常人肝组织和HepG2细胞中H1a和H1b的表达比例,以及在HBV、HCV感染情况下和肝癌组织中H1b表达水平的变化.
2.合成H1b特异性多肽并与钥孔戚血蓝素(KLH)偶联,免疫小鼠制备H1b特异性多克隆抗体,鉴定抗体的效价和特异性;亲和柱层析的方法从人血清和HepG2细胞培养上清中分离并纯化可溶性ASGPR,采用特异性抗体通过Western blot鉴定可溶性ASGPR的组成;免疫组织化学检测H1b在肝组织中表达和定位。
3.合成一个长度为115nt含有25个随机序列的单链DNA随机文库,通过体外转录构建出单链RNA适配子随机文库,从肝组织中分离纯化ASGPR大亚基作为靶蛋白,采用SELEX(systematic evolution of ligands by exponential enrichment)技术筛选高亲和力的ASGPR特异性RNA适配子;测序分析筛选适配子的序列,预测并分析其二级结构特点。
4.同位素~(32)p标记适配子,通过膜结合测定实验、凝胶阻滞实验鉴定筛选适配子对靶蛋白的特异性和亲和力;绿色荧光FITC标记适配子,鉴定其与肝细胞系HepG2和Huh7的特异性结合。
结果
1.人肝组织和肝细胞系HepG2中普遍表达ASGPR大亚基异构体H1a和H1b,H1b的cDNA较H1a缺失了一段117 nt的序列,该序列是ASGPR大亚基编码基因的第二个外显子,其两端具有典型的AG/GT序列,提示H1的两种异构体产生于对ASGPR mRNA的选择性剪接。
2.正常肝组织和HepG2细胞中H1a和H1b的表达比例分别为5.2:1和2.6:1,而且H1b的表达水平在HBV和HCV感染细胞中下降约60%,在肝癌组织中下降90%以上。
3.在从正常人血清和HepG2细胞培养上清中纯化的可溶性ASGPR蛋白中,可以检测到H1b蛋白单体以及H1b和H2构成的多聚体;对肝组织进行的免疫组织化学检测显示H1b不能定位至细胞膜,而主要存在于细胞质中。
4.经过12轮SELEX筛选,适配子文库中与靶蛋白结合的适配子得到明显富集;对第12轮文库中随机挑选的48个适配子进行测序并预测其二级结构,发现文库中适配子从结构上主要由两个家族构成,其占总适配子的比例分别为45.8%和33.3%;并找到一个适配子H1-A25与靶蛋白具有很高的亲和力,Kd值为48.79nM。
5、在膜结合测定实验和凝胶阻滞实验中,反应体系中不添加靶蛋白,或用无关蛋白替代靶蛋白,则不能检测到明显的适配子H1-A25和蛋白结合;而在反应体系中加入过量未标记适配子H1-A25,则能明显阻断放射标记适配子H1-A25与H1蛋白的结合。
6、FITC标记的适配子H1-A25能结合至肝癌细胞系HepG2和HuH-7,但不能结合不表达ASGPR的HeLa细胞;加入ASGPR的多克隆抗体可部分阻断荧光标记适配子H1-A25与HepG2细胞或HuH-7细胞结合,而加入过量未标记适配子H1-A25则几乎可以完全阻断荧光标记适配子H1-A25结合HepG2细胞的荧光信号。
结论
1.人肝组织及肝细胞系HepG2和Huh7中普遍表达ASGPR大亚基异构体H1a和H1b。
2.大亚基异构体H1b编码的蛋白为分泌型H1。
3.血清中的可溶性ASGPR是由分泌型的H1和H2构成的功能性复合物。
4.成功地筛选出了具有高亲和力的肝脏ASGPR特异性RNA适配子H1-A25。
5.适配子H1-A25能特异性靶向结合至肝细胞。
本研究的创新点及意义
1.首次发现人类肝脏去唾液酸糖蛋白受体大亚基H1存在剪接异构体H1b,并证明此剪接异构体编码的分泌型蛋白参与构成功能性的可溶性ASGPR,从而完善了对可溶性ASGPR的认识,并为进一步全面系统探讨ASGPR的生物学功能奠定了坚实的基础。
2.本研究首次筛选得到了肝细胞特异性的RNA适配子并鉴定了其功能,而对其进一步的改进和修饰将使其有望成为新的诊断和治疗肝脏疾病的靶向性试剂和药物载体。
Objective
1. To study the occurrence mechanism, expression level and protein characteristics of the major subunit variants of human asialoglycoprotein receptor, and lay a foundation for further study of the function of ASGPR and for hepatic targeting therapy through ASGPR.
2. To obtain RNA aptamer with high affinity and specificity to the human liver specific asialoglycoprotein receptor (ASGPR) and lay a foundation for developing new reagents or drugs for the diagnosis and the targeting treatment of liver diseases.
Methods
1. Two major subunit variants of ASGPR (H1a and H1b) were cloned from normal human liver tissues and HepG2 cells, the occurrence mechanism of variant H1b was analyzed by sequences comparison. The expression levels of H1a and H1b in normal liver tissues and HepG2 cells were determined by real-time fluorescence quantitative PCR, as well as the level changes in HBV or HCV infected cells and HCC tissues.
2. H1b specific peptide was synthesized and coupled with keyhole limpet hemocyanin (KLH) for immunization. Then H1b-KLH conjugation was injected into mouse subcutaneously to produce polyclonal antibody. The titer and specificity of the antibody were confirmed. Soluble ASGPR (sASGPR) in normal human sera or HepG2 cell supernatants were purified by lactose-agarose affinity chromatography, and the compositions of sASGPR were analyed by specific antibodies. The expression and location of protein H1b in liver tissues were also determined by immunohistochemistry.
3. A single-stranded 115 nucleotides (nt) random DNA library containing 25 random oligonucleotides was synthesized in vitro, then random RNA aptamers library was constructed by in vitro transcription. Aptamers that can specifically bind to human hepatic asialoglycoprotein receptor was isolated from the RNA random library by using the SELEX (systematic evolution of ligands by exponential enrichment) procedure. Selected aptamers were analyzed by sequencing, and the secondary structures of these aptamers were prediced and analyzed by using RNA Structure Program.
4. Aptamers were labeled by ~(32)P, then filter biding assay and gel shift assay were performed to determine the specificity and affinity of the selected aptamers. One apatamer was also labeled by FITC, and the binding between the aptamer and the human hepatoma cell lines HepG2 and HuH-7 were identified by fluorescent staining.
Results
1. Two variants of ASGPR H1, designated H1a and H1b, are extensively expressed in both human liver tissues and in human hepatoma cell lines HepG2 and Huh7. Cloning of ASGPR H1 splice variant cDNAs and subsequent sequence analysis revealed that they differ only in the presence of 117 nt. This 117 nt segment corresponds to exon 2 in the genomic sequence of ASGPR, and the typical AG/GT 5' consensus splice donor and acceptor sites were found at each end of the 117 nt segment, strongly suggesting that ASGPR H1b is generated by alternative splicing of ASGPR mRNA.
2. The ratio of ASGPR H1a to H1b was about 2.6:1 in normal human liver tissue and 5.2:1 in HepG2 cells. H1b expression were decreased by approximately 60% in HBV or HCV infected cells, and were decreased more than 90% in HCC tissues.
3. Both the H1b protein and a functional soluble ASGPR (sASGPR) composed of H1b and H2 were identified in both normal human sera and in the supernatant of HepG2 cells. Immunohistochemistry analysis shows that protein H1b in liver tissues can not accumulate at the cellular membrane, but in the cytoplasm.
4. Twelve rounds of selection and amplification were performed, and the aptamers which can bind to H1 were significantly enriched. Round 12 RNAs were amplified by RT-PCR and cloned. Forty-eight randomly picked plasmid clones were sequenced. The secondary structures of these aptamers were predicted with RNA Structure Program. Most aptamers of Round 12 RNAs were represented by only two kinds of structures, and their percentages of composition of Round 12 RNAs were 45.8% and 33.3%, respectively. One aptamer, H1-A25, was found to have high affinity to protein H1. the dissociation constant for the aptamer:H1 complex was estimated to be 48.79 nM.
5. While P~(32)-labeled H1-A25 significantly bound to H1 protein on the nitrocellulose filter (determined by nitrocellulose filter binding assay), its binding to HBsAg, the HBV S antigen that served as a negative control, was similar to that of probe alone. Furthermore, gel mobility shift assays also confirmed the specific binding of aptamer H1-A25 to H1 protein, as only recombinant H1 but not HBsAg, could cause the retardation of mobility of P~(32)-labeled H1-A25 probe. The addition of 100-fold excess unlabeled aptamer to the reaction system abolished the aptamer-H1 interaction.
6. FITC labeling H1-A25 specifically bound to the ASGPR-expressing hepatoma cell lines HepG2 and Huh-7. However, no binding was shown to the ASGPR-negative cell line HeLa. The fluorescence signal was significantly reduced by preincubating HepG2 cells with anti-H1 polyclonal antibody and can be nearly blocked by adding 100-fold excess unlabeled H1-A25.
Conclusions
1. Two variants of ASGPR H1, designated H1a and H1b, are extensively expressed in both human liver tissues and in human hepatoma cell lines HepG2 and Huh7.
2. The protein encoded by the H1b variant is a secreted form of H1.
3. sASGPR is a hetero-oligomeric complex of the secreted form of H1 and H2 and is able to bind a lactose-agarose substrate.
4. RNA aptamer H1-A25 that can specifically bind to human hepatic ASGPR with high affinity was successfully selected by using SELEX.
5. Aptamer H1-A25 can specifically bind to human hapatocytes.
Significances of the study
1. Our works provide the first evidence of the existence of splice variant H1b of human hepatic ASGPR H1, and prove that the protein encoded by the variant H1b is a secreted form of H1 which participates in the composing of sASGPR complex. The study improved the understanding of sASGPR, and laid a foundation for further comprehensive study of the function of ASGPR.
2. This is the first reported RNA aptamer which could bind to a human hepatic specific receptor. And this newly isolated aptamer could be modified to deliver imaging, diagnostic, and therapeutic agents targeted at hepatic parenchymal cells.
引文
[1]Kao JH,Chen DS.Global control of hepatitis B virus infection.Lancet Infect Dis,2002;2:395-403.
[2]Parkin DM,Bray F,Ferlay J,Pisani P.Estimating the world cancer burden:Globocan 2000.Int J Cancer.2001;94(2):153-6.
[3]Weigel PH,Yik JH.Glycans as endocytosis signals:the cases of the asialoglyco-protein and hyaluronan/chondroitin sulfate receptors.Biochim Biophys Acta.2002;1572(2-3):341-63.
[4]Geuze HJ,Slot JW,Strous GJ,et al.Intracellular site of asialoglycoprotein receptor-ligand uncoupling:double-label immunoelectron microscopy during receptor-mediated endocytosis.Cell 1983;32(1):277-87.
[5]Geuze HJ,Slot JW,Strous GJ,et al.Intracellular receptor sorting during endocytosis:comparative immunoelectron microscopy of multiple receptors in rat liver.Cell 1984;37(1):195-204.
[6]Geffen I.,Spiess M.Asialoglycoprotein receptor.Int Rev Cytol 1992;137B:181-219.
[7]Spiess M.The asialoglycoprotein receptor:a model for endocytic transport receptors.Biochemistry 1990;29(43):10009-18.
[8] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem.1985;260(4): 1979-82.
[9] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor:conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A.1985;82(19):6465-9.
[10]Paietta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver, Hepatology. 1992;15(3):395-402.
[11]Tolchinsky S, Yuk MH, Ayalon M, et al. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits: Role of a juxtamembrane pentapeptide. J Biol Chem. 1996;271(24):14496-503.
[12]Yago H, Kohgo Y, Kato J, et al. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology. 1995;21(2):383-8.
[13]Dizhe EB, Akifiev BN, Missul BV, et al. Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo.Biochemistry (Mosc). 2001;66(1):55-61.
[14] Wang S, Cheng L, Yu F, et al. Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects. Int J Pharm. 2006;311(1-2):82-8.
[15] Di Stefano G, Kratz F, Lanza M, et al. Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier. Dig Liver Dis. 2003;35(6):428-33.
[16]Fiume L, Di Stefano G, Busi C, et al. Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate. J Hepatol. 1997;26(2):253-9.
[17]Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990;249(4968):505-10.
[18] Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands.Nature 1990;346(6287):818-22.
[19]Brody EN, Gold L. Aptamers as therapeutic and diagnostic agents, J. Biotechnol 2000;74(1):5-13.
[20]Hicke BJ, Stephens AW. Escort aptamers: a delivery service for diagnosis and therapy. J.Clin. Invest 2000; 106(8):923-8.
[21]Jayasena SD. Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem 1999;45(9): 1628-50.
[1] Ashwell G, Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem 1982;51:531-54.
[2] Schwartz AL. The hepatic asialoglycoprotein receptor. CRC Crit Rev Biochem 1984;16(3):207-33.
[3] Stockert RJ, Morell AG. Hepatic binding protein: the galactose-specific receptor of mammalian hepatocytes. Hepatology 1983 Sep-Oct;3(5):750-7.
[4] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci U S A 1985 Oct;82(19):6465-9.
[5] Bischoff J, Lodish HF. Two asialoglycoprotein receptor polypeptides in human hepatoma cells. J Biol Chem 1987 Aug 25;262(24): 11825-32.
[6] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. J Biol Chem 1985 Feb 25;260(4): 1979-82.
[7] Chiacchia KB, Drickamer K. Direct evidence for the transmembrane orientation of the hepatic glycoprotein receptors. J Biol Chem 1984 Dec 25;259(24): 15440-6.
[8] Paierta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver. Hepatology 1992 Mar;15(3):395-402.
[9] Tolchinsky S, Yuk MH, Ayalon M, Lodish HF, Lederkremer GZ. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits. Role of a juxtamembrane pentapeptide. J Biol Chem 1996 Jun 14;271(24): 14496-503.
[10]Yago H, Kohgo Y, Kato J, Watanabe N, Sakamaki S, Niitsu Y. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology 1995 Feb;21(2):383-8.
[11] Hardy MR, Townsend RR, Parkhurst SM, Lee YC. Different modes of ligand binding to the hepatic galactose/N-acetylgalactosamine lectin on the surface of rabbit hepatocytes. Biochemistry 1985 Jan 1;24(1):22-8.
[12] Oka JA, Herzig MC, Weigel PH. Functional galactosyl receptors on isolated rat hepatocytes are hetero-oligomers. Biochem Biophys Res Commun 1990 Aug 16;170(3):1308-13.
[13] Ruiz NI, Drickamer K. Differential ligand binding by two subunits of the rat liver asialoglycoprotein receptor. Glycobiology 1996 Jul;6(5):551-9.
[14]Braiterman LT, Chance SC, Porter WR, Lee YC, Townsend RR, Hubbard AL. The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor. J Biol Chem 1989 Jan 25;264(3): 1682-8.
[15]Halberg DF, Wager RE, Farrell DC, Hildreth J 4th, Quesenberry MS, Loeb JA, et al. Major and minor forms of the rat liver asialoglycoprotein receptor are independent galactose-binding proteins. Primary structure and glycosylation heterogeneity of minor receptor forms. J Biol Chem 1987 Jul 15;262(20):9828-38.
[16]Bider MD, Cescato R, Jeno P, Spiess M. High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2. Eur J Biochem 1995 May 15;230(1):207-12.
[17]Saxena A, Yik JH, Weigel PH. H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid. J Biol Chem 2002 Sep 20;277(38):35297-304.
[18] Spiess M, Lodish HF. An internal signal sequence: the asialoglycoprotein receptor membrane anchor. Cell 1986 Jan 17;44(1): 177-85.
[19] Spiess M, Handschin C. Deletion analysis of the internal signal-anchor domain of the human asialoglycoprotein receptor H1. EMBO J 1987 Sep;6(9):2683-91.
[20] Weigel PH, Yik JH. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta 2002 Sep 19;1572(2-3):341-63.
[21] Weigel PH. Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors. Bioessays 1994 Jul; 16(7):519-24.
[22] Becker S, Spiess M, Klenk HD. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol 1995 Feb;76 ( Pt 2):393-9.
[23]Treichel U, Meyer zum Buschenfelde KH, Dienes HP, Gerken G. Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol 1997;142(3):493-8.
[24]Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD. Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 2003 Jan;77(1):546-59.
[25]Dotzauer A, Gebhardt U, Bieback K, Gottke U, Kracke A, Mages J, et al. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol 2000 Dec;74(23): 10950-7.
[26]McFarlane BM, McSorley CG, Vergani D, McFarlane IG, Williams R. Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. J Hepatol 1986;3(2): 196-205.
[27]Treichel U, Poralla T, Hess G, Manns M, Meyer zum Biischenfelde KH. Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology 1990 Apr;11(4):606-12.
[28]Treichel U, Gerken G, Rossol S, Rotthauwe HW, Meyer zum Buschenfelde KH, Poralla T. Autoantibodies against the human asialoglycoprotein receptor: effects of therapy in autoimmune and virus-induced chronic active hepatitis. J Hepatol 1993 Aug;19(1):55-63.
[29]Hilgard P, Schreiter T, Stockert RJ, Gerken G, Treichel U. Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis. Hepatology 2004 May;39(5): 1398-407.
[1] Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990;249(4968):505-10.
[2] Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands.Nature 1990;346(6287):818-22.
[3] Brody EN, Gold L. Aptamers as therapeutic and diagnostic agents, J. Biotechnol 2000;74(1):5-13.
[4] Hicke BJ, Stephens AW. Escort aptamers: a delivery service for diagnosis and therapy. J.Clin. Invest 2000;106(8):923-8.
[5] Jayasena SD. Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem 1999;45(9): 1628-50.
[6] Geffen I., Spiess M. Asialoglycoprotein receptor. Int Rev Cytol 1992; 137B:181-219.
[7] Spiess M. The asialoglycoprotein receptor: a model for endocytic transport receptors.Biochemistry 1990;29(43): 10009-18.
[8] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem.1985;260(4): 1979-82.
[9] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A.1985;82(19):6465-9.
[10]Rhodes A, Deakin A, Spaull J, Coomber B, Aitken A, Life P, Rees S. The generation and characterization of antagonist RNA aptamers to human oncostatin M. J Biol Chem. 2000 Sep 15;275(37):28555-61.
[11]Pagratis NC, Bell C, Chang YF, Jennings S, Fitzwater T, Jellinek D, Dang C. Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor. Nat Biotechnol. 1997 Jan;15(1):68-73.
[12]Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature. 2002 Sep 5;419(6902):90-4.
[13] Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature. 1992 Feb 6;355(6360):564-6.
[14] Wiegand TW, Williams PB, Dreskin SC, Jouvin MH, Kinet JP, Tasset D. High-affinity oligonucleotide ligands to human IgE inhibit binding to Fc epsilon receptor I. J Immunol.1996 Jul 1;157(1):221-30.
[15] Watson SR, Chang YF, O'Connell D, Weigand L, Ringquist S, Parma DH. Anti-L-selectin aptamers: binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo. Antisense Nucleic Acid Drug Dev. 2000 Apr;10(2):63-75.
[16] Chapman JA, Beckey C. Pegaptanib: A novel approach to ocular neovascularization. Ann Pharmacother. 2006 Jul-Aug;40(7-8): 1322-6.
[17]Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov. 2006 Feb;5(2): 123-32.
[18]McNamara JO 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol. 2006 Aug;24(8):1005-15.
[19]Chu TC, Twu KY, Ellington AD, Levy M. Aptamer mediated siRNA delivery. Nucleic Acids Res. 2006 Jun l;34(10):e73.
[20] Weigel PH, Yik JH. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta. 2002 Sep 19;1572(2-3):341-63.
[1]Weigel PH,Yik JH.Glycans as endocytosis signals:the cases of the asialoglyco-protein and hyaluronan/chondroitin sulfate receptors.Biochim Biophys Acta.2002 Sep 19;1572(2-3):341-63.
[2]Geuze HJ,Slot JW,Strous GJ,Lodish HF,Schwartz AL.Intracellular site of asialoglycoprotein receptor-ligand uncoupling:double-label immunoelectron microscopy during receptor-mediated endocytosis.Cell 1983 Jan;32(1):277-87.
[3]Geuze HJ,Slot JW,Strous GJ,Peppard J,von Figura K,Hasilik A,Schwartz AL.Intracellular receptor sorting during endocytosis:comparative immunoelectron microscopy of multiple receptors in rat liver.Cell 1984 May;37(1):195-204.
[4]Geffen I.,Spiess M.Asialoglycoprotein receptor.Int Rev Cytol.1992;137B:181-219.
[5]Spiess M.The asialoglycoprotein receptor:a model for endocytic transport receptors.Biochemistry 1990 Oct 30;29(43):10009-18.
[6]Ashwell G.,Harford J.Carbohydrate-specific receptors of the liver.Ann.Rev.Biochem.1982;51:531-54.
[7]Stockert RJ,Morell AG..Hepatic binding protein:the galactose-specific receptor of mammalian hepatocytes. Hepatology, 1983 Sep-Oct;3(5):750-7.
[8] Ashwell G, Morell AG. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv. Enzymol. 1974;41(0):99-128.
[9] Weigel PH, Schmell E, Lee YC, Roseman S. Specific adhesion of rat hepatocytes to beta-galactosides linked to polyacrylamide gels. J Biol Chem. (1978) 1978 Jan 25;253 (2):330-3.
[10]Schnaar RL, Weigel PH, Kuhlenschmidt MS, Lee YC, Roseman S. Adhesion of chicken hepatocytes to polyacrylamide gels derivatized with N-acetylglucosamine. J Biol Chem.1978 Nov 10;253(21):7940-51.
[11]Baenziger JU, Maynard Y. Human hepatic lectin: Physiochemical properties and specificity. J Biol Chem. 1980 May 25;255(10):4607-13.
[12]Ciechanover A, Schwartz AL, Lodish HF, Sorting and recycling of cell surface receptors and endocytosed ligands: the C and transferrin receptors, J Cell Biochem.1983;23(1-4):107-30.
[13]Abdullah M, Widgren EE, O'Rand MG. A mammalian sperm lectin related to rat hepatocyte lectin-2/3. Purification from rabbit testis and identification as a zona binding protein. Mol. Cell. Biochem. 1991 May 15;103(2):155-61.
[14]Goluboff ET, Mertz JR, Tres LL, Kierszenbaum AL. Galactosyl receptor in human testis and sperm is antigenically related to the minor C-type (Ca(2+)-dependent) lectin variant of human and rat liver. Mol Reprod Dev. 1995 Apr;40(4):460-6.
[15]Pacifico F, Liguoro D, Acquaviva R, Formisano S, Consiglio E. Thyroglobulin binding and TSH regulation of the RHL-1 subunit of the asialoglycoprotein receptor in rat thyroid. Biochimie. 1999May;81(5):493-6.
[16]Kolb-Bachofen V, Schlepper-Sch(a|¨)fer J, Vogell W, Kolb H. Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis. Cell. 1982 Jul;29(3):859-66.
[17]Ii M, Kurata H, Itoh N, Yamashina I, Kawasaki T. Molecular cloning and sequence analysis of cDNA encoding the macrophage lectin specific for galactose and N-acetylgalactosamine. J Biol Chem. 1990 Jul 5;265(19):11295-8.
[18]Mu JZ, Fallon RJ, Swanson PE, Carroll SB, Danaher M, Alpers DH. Expression of an endogenous asialoglycoprotein receptor in a human intestinal epithelial cell line, Caco-2, Biochim. Biophys. Acta 1994 Jul 21;1222(3):483-91.
[19]Valladeau J, Duvert-Frances V, Pin JJ. Kleijmeer MJ. Ait-Yahia S, Ravel O, Vincent C,Vega F Jr, Helms A, Gorman D. Zurawski SM, Zurawski G, Ford J, Saeland S. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 2001 Nov 15; 167(10):5767-74.
[20]Seow YY, Tan MG, Woo KT. Expression of a functional asialoglycoprotein receptor in human renal proximal tubular epithelial cells. Nephron. 2002 Jul;91(3):431-8.
[21] Schwartz AL. The hepatic asialoglycoprotein receptor. CRC Crit. Rev. Biochem.1984;16(3):207-33.
[22]Breitfeld PP, Simmons CF Jr, Strous GJ, Geuze HJ, Schwartz AL. Cell biology of the asialoglycoprotein receptor system: a model of receptor-mediated endocytosis. Int Rev Cytol. 1985;97:47-95.
[23]Kawasaki T, Ashwell G. Carbohydrate structure of glycopeptides isolated from an hepatic membrane-binding protein specific for asialoglycoproteins, J. Biol. Chem. 1976 Sep 10;251(17):5292-9.
[24]Sanford JP, Doyle D. Mouse asialoglycoprotein receptor cDNA sequence: conservation of receptor genes during mammalian evolution. Biochim Biophys Acta. 1990 Oct 23;1087(2):259-61.
[25]Takezawa R, Shinzawa K, Watanabe Y, Akaike T. Determination of mouse major asialoglycoprotein receptor cDNA sequence. Biochim Biophys Acta. 1993 Feb 20;1172(l-2):220-2.
[26]Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem. 1985 Feb 25;260(4):1979-82.
[27]Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A. 1985 Oct;82(19):6465-9.
[28]Drickamer K, Mamon JF, Binns G, Leung JO. Primary structure of the rat liver asialoglycoprotein receptor. Structural evidence for multiple polypeptide species, J Biol Chem. 1984 Jan 25;259(2):770-8. [29]Herzig MC, Weigel PH. Surface and internal galactosyl receptors are heterooligomers and retain this structure after ligand internalization or receptor modulation. Biochemistry.1990 Jul 10;29(27):6437-47.
[30]Paietta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver, Hepatology. 1992 Mar;15(3):395-402.
[31]Yik JH, Saxena A, Weigel PH. The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-ligomeric receptor complexes. J Biol Chem. 2002 Jun 21;277(25):23076-83. Epub 2002 Apr 9.
[32]Tolchinsky S, Yuk MH, Ayalon M, Lodish HF, Lederkremer GZ. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits: Role of a juxtamembrane pentapeptide. J Biol Chem. 1996 Jun 14;271(24):14496-503.
[33]Yago H, Kohgo Y, Kato J, Watanabe N, Sakamaki S, Niitsu Y. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology. 1995 Feb;21(2):383-8.
[34]Chiacchia KB, Drickamer K. Direct evidence for the transmembrane orientation of the hepatic glycoprotein receptors. J Biol Chem. 1984 Dec 25;259(24): 15440-6.
[35]Fuhrer C, Geffen I, Huggel K, Spiess M. The two subunits of the asialoglycoprotein receptor contain different sorting information. J Biol Chem. 1994 Feb 4;269(5):3277-82.
[36]Bider MD, Wahlberg JM, Kammerer RA, Spiess M. The oligomerization domain of the asialoglycoprotein receptor preferentially forms 2:2 heterotetramers in vitro. J Biol Chem. 1996 Dec 13;271 (50):31996-2001.
[37] Meier M, Bider MD, Malashkevich VN, Spiess M, Burkhard P. Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. J Mol Biol. 2000 Jul 21;300(4):857-65.
[38]Hardy MR, Townsend RR, Parkhurst SM, Lee YC. Different modes of ligand binding to the hepatic galactose/N-acetylgalactosamine lectin on the surface of rabbit hepatocytes.Biochemistry. 1985 Jan 1;24(1):22-8.
[39] Oka JA, Herzig MC, Weigel PH. Functional galactosyl receptors on isolated rat hepatocytes are hetero-oligomers. Biochem Biophys Res Commun. 1990 Aug 16;170(3):1308-13.
[40]Braiterman LT, Chance SC, Porter WR. Lee YC, Townsend RR, Hubbard AL. The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor. J Biol Chem. 1989 Jan 25;264(3):1682-8.
[41]Halberg DF, Wager RE, Farrell DC, Hildreth J 4th, Quesenberry MS, Loeb JA, Holland EC, Drickamer K. Major and minor forms of the rat liver asialoglycoprotein receptor are independent galactose-binding proteins. Primary structure and glycosylation heterogeneity of minor receptor forms. J Biol Chem. 1987 Jul 15;262(20):9828-38.
[42]Bider MD, Cescato R, Jeno P, Spiess M. High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2. Eur J Biochem. 1995 May 15;230(1):207-12.
[43]Saxena A, Yik JH, Weigel PH. H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid. J Biol Chem. 2002 Sep 20;277(38):35297-304. Epub 2002 Jun 27.
[44] Collins JC, Stockert RJ, Morell AG. Asialoglycoprotein receptor expression in murine pregnancy and development. Hepatology, 1984 Jan-Feb;4(l):80-3.
[45]Petell JK, Doyle D. Developmental regulation of the hepatocyte receptor for galactose-terminated glycoproteins. Arch Biochem Biophys. 1985 Sep;241(2):550-60.
[46]Collins JC, Paietta E, Green R, Morell AG, Stockert RJ. Biotin-dependent expression of the asialoglycoprotein receptor in HepG2. J Biol Chem. 1988 Aug 15;263(23):11280-3.
[47] Stockert RJ. The asialoglycoprotein receptor: relationships between structure, function,and expression. Physiol Rev. 1995 Jul;75(3):591-609.
[48]Braun JR, Willnow TE, Ishibashi S, Ashwell G, Herz J. The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit. J Biol Chem. 1996 Aug 30;271(35):21160-6.
[49]Tozawa R, Ishibashi S, Osuga J, Yamamoto K, Yagyu H, Ohashi K, Tamura Y, Yahagi N, Iizuka Y, Okazaki H, Harada K, Gotoda T, Shimano H, Kimura S, Nagai R, Yamada N.Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit. Its obligate requirement for the stable expression of oligomeric receptor. J Biol Chem. 2001 Apr 20;276( 16): 12624-8. Epub 2001 Jan 16.
[50] Windier E, Greeve J, Levkau B, Kolb-Bachofen V, Daerr W, Greten H. The human asialoglycoprotein receptor is a possible binding site for low-density lipoproteins and chylomicron remnants. Biochem J. 1991 May 15;276 (Pt 1):79-87.
[51]Rotundo RF, Rebres RA, Mckeown-Longo PJ, Blumenstock FA, Saba TM. Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor:possible pathway for fibronectin deposition and turnover in the rat liver. Hepatology. 1998 Aug;28(2):475-85.
[52]Weigel PH. Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors. BioEssays. 1994 Jul;16(7):519-24.
[53] Becker S, Spiess M, Klenk HD. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol. 1995 Feb;76 ( Pt 2):393-9.
[54]Treichel U, Meyer zum Buschenfelde KH, Dienes HP, Gerken G. Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol. 1997;142(3):493-8.
[55]Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD. Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol. 2003 Jan;77(1):546-59.
[56]Dotzauer A, Gebhardt U, Bieback K, Gottke U, Kracke A, Mages J, Lemon SM, Vallbracht A. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol. 2000 Dec;74(23): 10950-7.
[57]U. Treichel , T. Poralla , G. Hess , M. Manns , K.H. Meyer zum Buschenfelde .Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology. (1990) Apr;11(4):606-12.
[58]Treichel U, Poralla T, Hess G, Manns M, Meyer zum Buschenfelde KH.Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis.Hepatology. 1990 Apr;11(4):606-12.
[59]Dizhe EB, Akifiev BN, Missul BV, Orlov SV, Kidgotko OV, Sukonina VE, Denisenko AD, Perevozchikov AP. Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo. Biochemistry (Mosc). 2001 Jan;66(1):55-61.
[60]Wang S, Cheng L, Yu F, Pan W, Zhang J. Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects. Int J Pharm. 2006 Mar 27;311(1-2):82-8. Epub 2006 Jan 19.
[61] Peng DJ, Sun J, Wang YZ, Tian J, Zhang YH, Noteborn MH, Qu S. Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor. Cancer Gene Ther. 2007 Jan;14(1):66-73. Epub 2006 Jul 28.
[62] Di Stefano G, Kratz F, Lanza M, Fiume L. Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier. Dig Liver Dis. 2003 Jun;35(6):428-33.
[63] Di Stefano G, Fiume L, Domenicali M, Busi C, Chieco P, Kratz F, Lanza M, Mattioli A,Pariali M, Bernardi M. Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis. Dig Liver Dis. 2006 Jun;38(6):404-8. Epub 2006 Apr 3.
[64] Fiume L, Di Stefano G, Busi C, Mattioli A, Battista Gervasi G, Bertini M, Bartoli C,Catalani R, Caccia G, Farina C, Fissi A, Pieroni O, Giuseppetti R, D'Ugo E, Bruni R,Rapicetta M. Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate. J Hepatol. 1997 Feb;26(2):253-9.
[65] Yang J, Bo XC, Ding XR, Dai JM, Zhang ML, Wang XH, Wang SQ. Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication. J Viral Hepat. 2006 Mar; 13(3): 158-65.
[66]Nomura Y, Yamasaki K, Sakamoto S, Hayasi N, Hosaka K, Fukusima K, Sugimura K,Sakai H, Nagai H. A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model. Kaku Igaku. 2000 Nov;37(6):631-8.
[1]Kao JH,Chen DS.Global control of hepatitis B virus infection.Lancet Infect Dis,2002;2:395-403.
[2]Parkin DM,Bray F,Ferlay J,Pisani P.Estimating the world cancer burden:Globocan 2000.Int J Cancer.2001;94(2):153-6.
[3]Ashwell G.,Morell AG..The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins.Adv.Enzymol.1974;41(0):99-128.
[4]Nishikawa M,Miyazaki C.Yamashita F,Takakura Y,Hashida M.Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties.Am J Physiol.1995 May;268(5 Pt 1):G849-56.
[5]蔡春,苏敏,杨健,等.肝靶向前药半乳糖化人血清白蛋白氟尿嘧啶偶联物的合成及靶向作用.中国药学杂志,2006,41(10):786-789.
[6]Di Stefano G,Kratz F,Lanza M,Fiume L.Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier.Dig Liver Dis.2003 Jun;35(6):428-33.
[7]Di Stefano G,Fiume L,Domenicali M,Busi C,Chieco P,Kratz F,Lanza M,Mattioli A,Pariali M,Bernardi M.Doxorubicin coupled to lactosaminated albumin:Effects on rats with liver fibrosis and cirrhosis.Dig Liver Dis.2006 Jun;38(6):404-8.Epub 2006 Apt 3.
[8]Nomura Y,Yamasaki K,Sakamoto S,Hayasi N,Hosaka K,Fukusima K,Sugimura K,Sakai H,Nagai H.A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model.Kaku Igaku.2000 Nov;37(6):631-8.
[9]钟森,温守明,张定凤,等.乳糖化多聚赖氨酸导向反义寡核苷酸抗乙型肝炎病毒的作用.中华实验和临床病毒学杂志,2001,15(2):150-153.
[10]Dizhe EB,Akifiev BN,Missul BV,Orlov SV,Kidgotko OV,Sukonina VE,Denisenko AD,Perevozchikov AP.Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo.Biochemistry(Mosc).2001 Jan;66(1):55-61.
[11]Wang S,Cheng L,Yu F,Pan W,Zhang J.Delivery,of different length poly(L-lysine)conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects.Int J Pharm.2006 Mar 27;311(1-2):82-8.Epub 2006Jan 19.
[12]Peng DJ,Sun J,Wang YZ,Tian J,Zhang YH,Notebom MH,Qu S.Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor.Cancer Gene Ther.2007 Jan;14(1):66-73.Epub 2006 Jul 28.
[]3]王学东,冯永堂,陈相英,等.乳糖化赖氨酸与反义X基因质粒复合物体外对HBV表达的抑制.中国生化药物杂志,2005,26(4):205-207.
[14]Fiume L,Di Stefano G,Busi C,Mattioli A,Battista Gervasi G,Bertini M,Bartoli C,Catalani R,Caccia G,Farina C,Fissi A,Pieroni O,Giuseppetti R,D'Ugo E,Bruni R,Rapicetta M.Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine.Synthesis of the carrier and pharmacological properties of the conjugate.J Hepatol.1997 Feb;26(2):253-9.
[15]Hashida M,Hirabayashi H,Nishikawa M,Takakura Y..Targeted delivery of drugs and proteins to the liver via receptor-mediated endocytosis.J Controlled Release,1997,46(1-2):129-137.
[16]Gao S,Chen J,Dong L,Ding Z,Yang YH,Zhang J.Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector.Eur J Pharm Biopharm.2005 Aug;60(3):327-34.
[17]Mi FL,Yu SH,Peng CK,et al.Synthesis and characterization of a novel glycoconjugated macromolecule.Polymer,2006,47(12):4348-4358.
[]8]黄容琴,裴元英.主动肿瘤靶向给药系统的研究进展.中国医药工业杂志,2005,36(8):505-510.
[19]侯新朴,王黎,王向涛,等.脂质体肝实质细胞靶向性研究.药学学报,2003,38(2):143-146.
[20]Biessen EA,Bakkeren HF,Beuting DM,Kuiper J,Van Berkel TJ.Ligand size is a major determinant of high-affinity binding of fucose-and galactose-exposing(lipo)proteins by the hepatic fucose receptor.Biochem J,1994,299(Pt 1):291-296.
[21]Higuchi Y,Nishikawa M,Kawakami S,Yamashita E Hashida M.Uptake characteristics of mannosylated and fucosylated bovine serum albumin in primary cultured rat sinusoidal endothelial cells and Kupffer cells.In J Pharm,2004,287(1-2):147-154.
[22]Weiss SI,Sieverling N,Niclasen M,Maucksch C,Th(u|¨)nemann AE M6hwald H,Reinhardt D,Rosenecker J,Rudolph C.Uronic acids functionalized polyethyleneimine (PEI)-polyethyleneglycol(PEG)-grafl-copolymers as novel synthetic gene carriers.Biomaterials,2006,27(10):2302-2312.
[23]Opanasopit P,Sakai M,Nishikawa M,Kawakami S,Yarnashita E Hashida M.Inhibition of liver metastasis by targeting of irnmunomodulators using mannosylated liposome carriers.J Controlled Release,2002,80(1-3):283-294.
[24]Dierling AM,Cui ZR.Targeting primaquine into liver using chylomicron emulsions for potential vivax malaria therapy.Int J Pharm,2005,303(1-2):143-152.
[25]Jansen RW,Molema G,Harms G,Kruijt JK,van Berkel YJ,Hardonk MJ,Meijer DK.Formaldehyde treated albumin contains monomeric and polymeric forms that are differently cleared by endothelial and Kupffer cells of the liver:evidence for scavenger receptor heterogeneity.Biochem Biophys Res Commun,1991,180(1):23-32.
[26]Furitsu H,Ogawara K,Fujita T,et al.Pharmacokinetic analysis of scavenger receptor-mediated uptake of anionized proteins in the isolated perfused rat liver.Int J Pharm,1997,151(1):15-26.
[27]高 艳,李厚丽,吕青志,翟光喜.主动转运途径在肝靶向给药系统中的应用.中国医药工业杂志,2008,39(7):542-547.
[28]Beljaars L,Molema G,Weert B,Bonnema H,Olinga P,Groothuis GM,Meijer DK,Poelstra K.Albumin Modified With Mannose 6-Phosphate:A Potential Carrier for Selective Delivery of Antifibrotic Drugs to Rat and Human Hepatic Stellate Cells.Hepatology,1999,29(5):1486-1493.
[29]张其胜,Luk JM,张健,等.甘草次酸靶向肝星状细胞治疗肝纤维化的体内研究。中华肝脏病杂志,2005,13(9):664-667.
[30]Greupink R,Bakker HI,Reker-Smit C,van Loenen-Weemaes AM,Kok RJ,Meijer DK, Beljaars L,Poelstra K.Studies on the targeted delivery,of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell.J Hepatol,2005,43(5):884-892.
[31]Adrian JE,Kamps JA,Scherphof GL,Meijer DK,van Loenen-Weemaes AM,Reker-Smit C,Terpstra P,Poelstra K.A novel lipidbased drug carrier targeted to the non-parenchymal cells,including hepatic stellate cells,in the fibrotic livers of bile duct ligated rats.Biochim BiophyActa,2007,1768(6):1430-1439.
[32]杜施霖,王吉耀,潘弘,等.含有RGD序列环肽介导的干扰素脂质体对大鼠肝纤维化的治疗作用.中华医学杂志,2005,85(15):1015-1020.
[33]Nada H,Wu CH,Wu GY.Chemical modifi-canon of an ecotropic marine leukemia virus results in redirection of its target cell speci-ficity.J Biol Chem,1991,266;14143-14146.
[34]Cristiano W,Smith LC,Woo SI.Hepatic gene therapy;adenovirus enhancement of receptomediated gene delivery and expression in ptvrtaty hepatocytes.Proc Natl Acad Sci USA,1993,90:2122-2126.
[35]Kaneda Y,Saeki Y,Morishita R.Gene therapy using HVJIiposomes:the best of both worlds? Mol Med Today,1999.5(7):298-303
[36]Limuro Y,Fujimoto J.Strategy of gene therapy for liver cirrhosis and hepatocellular carcinoma.J Hepatobiliary Pancreat Surg,2003,10(1):45-47.
[37]Hazra B,Pore V,Dey S,Datta S,Darokar M,Saikia D,Khanuja SP,Thakur A.Bile acid amides derived from chiral amino alcohols:novel antimicrobials and antifungals.Bioorg Med Chem Lett,2004,14(3):773-777.
[38]Tu N,Link JT,Sorensen BK,Emery M,Grynfarb M.Goos-Nilsson A,Nguyen B.Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator.Bioorg Med Chem Lett,2004,14(16):4179-4183.
[39]Fiorucci S,Antonelli E,Brancaleone V,Sanpaolo L,Orlandi S,Distrutti E,Acuto G,Clerici C,Baldoni M,Del Soldato P,Morelli A.NCX-1000,a nitric oxide-releasing derivative of ursodeoxycholic acid,ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver.J Hepatol,2003,39(6):932-939.
[40]陈莉,蒋丽媛,张奕华.NCX-1000的新合成方法.药学进展,2003,27(6):358-360.
[41]Erion MD,van Poelje PD,Mackenna DA,Colby TJ,Montag AC,Fujitaki JM,Linemeyer DL, Bullough DA. Liver Targeted Drug Delivery Using HepDirectl Prodrugs. J Pharmacol Exp Then 2005, 312 (2): 554-560.
[42] Lin CC, Fang C, Benetton S, Xu GF, Yeh LT. Metabolic activation of pradefovir by CYP3A4 and its potential as an inhibitor or inducer. Antimicrob Agents Chemother, 2006,50 (9): 2926-2931.
[43]Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Then 1999, 6 (7): 1258-1266.
[44] Zhang G, Song YK, Liu D. Long-term expression DNA using a hydrodynamics-based procedure. Gene Ther, 2000,7 (15): 1344-1349.
[45]Kobayashi N, Kuramoto I, Yamaoka K, Hashida M, Takakura Y. Hepatic Uptake and Gene Expression Mechanisms following Intravenous Administration of Plasmid DNA by Conventional and Hydrodynamics-Based Procedures. J Pharmacol Exp Ther, 2001,297(3): 853-860.
[2]Parkin DM,Bray F,Ferlay J,Pisani P.Estimating the world cancer burden:Globocan 2000.Int J Cancer.2001;94(2):153-6.
[3]Weigel PH,Yik JH.Glycans as endocytosis signals:the cases of the asialoglyco-protein and hyaluronan/chondroitin sulfate receptors.Biochim Biophys Acta.2002;1572(2-3):341-63.
[4]Geuze HJ,Slot JW,Strous GJ,et al.Intracellular site of asialoglycoprotein receptor-ligand uncoupling:double-label immunoelectron microscopy during receptor-mediated endocytosis.Cell 1983;32(1):277-87.
[5]Geuze HJ,Slot JW,Strous GJ,et al.Intracellular receptor sorting during endocytosis:comparative immunoelectron microscopy of multiple receptors in rat liver.Cell 1984;37(1):195-204.
[6]Geffen I.,Spiess M.Asialoglycoprotein receptor.Int Rev Cytol 1992;137B:181-219.
[7]Spiess M.The asialoglycoprotein receptor:a model for endocytic transport receptors.Biochemistry 1990;29(43):10009-18.
[8] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem.1985;260(4): 1979-82.
[9] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor:conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A.1985;82(19):6465-9.
[10]Paietta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver, Hepatology. 1992;15(3):395-402.
[11]Tolchinsky S, Yuk MH, Ayalon M, et al. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits: Role of a juxtamembrane pentapeptide. J Biol Chem. 1996;271(24):14496-503.
[12]Yago H, Kohgo Y, Kato J, et al. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology. 1995;21(2):383-8.
[13]Dizhe EB, Akifiev BN, Missul BV, et al. Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo.Biochemistry (Mosc). 2001;66(1):55-61.
[14] Wang S, Cheng L, Yu F, et al. Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects. Int J Pharm. 2006;311(1-2):82-8.
[15] Di Stefano G, Kratz F, Lanza M, et al. Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier. Dig Liver Dis. 2003;35(6):428-33.
[16]Fiume L, Di Stefano G, Busi C, et al. Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate. J Hepatol. 1997;26(2):253-9.
[17]Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990;249(4968):505-10.
[18] Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands.Nature 1990;346(6287):818-22.
[19]Brody EN, Gold L. Aptamers as therapeutic and diagnostic agents, J. Biotechnol 2000;74(1):5-13.
[20]Hicke BJ, Stephens AW. Escort aptamers: a delivery service for diagnosis and therapy. J.Clin. Invest 2000; 106(8):923-8.
[21]Jayasena SD. Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem 1999;45(9): 1628-50.
[1] Ashwell G, Harford J. Carbohydrate-specific receptors of the liver. Annu Rev Biochem 1982;51:531-54.
[2] Schwartz AL. The hepatic asialoglycoprotein receptor. CRC Crit Rev Biochem 1984;16(3):207-33.
[3] Stockert RJ, Morell AG. Hepatic binding protein: the galactose-specific receptor of mammalian hepatocytes. Hepatology 1983 Sep-Oct;3(5):750-7.
[4] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution. Proc Natl Acad Sci U S A 1985 Oct;82(19):6465-9.
[5] Bischoff J, Lodish HF. Two asialoglycoprotein receptor polypeptides in human hepatoma cells. J Biol Chem 1987 Aug 25;262(24): 11825-32.
[6] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA. An internal signal sequence for membrane insertion. J Biol Chem 1985 Feb 25;260(4): 1979-82.
[7] Chiacchia KB, Drickamer K. Direct evidence for the transmembrane orientation of the hepatic glycoprotein receptors. J Biol Chem 1984 Dec 25;259(24): 15440-6.
[8] Paierta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver. Hepatology 1992 Mar;15(3):395-402.
[9] Tolchinsky S, Yuk MH, Ayalon M, Lodish HF, Lederkremer GZ. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits. Role of a juxtamembrane pentapeptide. J Biol Chem 1996 Jun 14;271(24): 14496-503.
[10]Yago H, Kohgo Y, Kato J, Watanabe N, Sakamaki S, Niitsu Y. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology 1995 Feb;21(2):383-8.
[11] Hardy MR, Townsend RR, Parkhurst SM, Lee YC. Different modes of ligand binding to the hepatic galactose/N-acetylgalactosamine lectin on the surface of rabbit hepatocytes. Biochemistry 1985 Jan 1;24(1):22-8.
[12] Oka JA, Herzig MC, Weigel PH. Functional galactosyl receptors on isolated rat hepatocytes are hetero-oligomers. Biochem Biophys Res Commun 1990 Aug 16;170(3):1308-13.
[13] Ruiz NI, Drickamer K. Differential ligand binding by two subunits of the rat liver asialoglycoprotein receptor. Glycobiology 1996 Jul;6(5):551-9.
[14]Braiterman LT, Chance SC, Porter WR, Lee YC, Townsend RR, Hubbard AL. The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor. J Biol Chem 1989 Jan 25;264(3): 1682-8.
[15]Halberg DF, Wager RE, Farrell DC, Hildreth J 4th, Quesenberry MS, Loeb JA, et al. Major and minor forms of the rat liver asialoglycoprotein receptor are independent galactose-binding proteins. Primary structure and glycosylation heterogeneity of minor receptor forms. J Biol Chem 1987 Jul 15;262(20):9828-38.
[16]Bider MD, Cescato R, Jeno P, Spiess M. High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2. Eur J Biochem 1995 May 15;230(1):207-12.
[17]Saxena A, Yik JH, Weigel PH. H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid. J Biol Chem 2002 Sep 20;277(38):35297-304.
[18] Spiess M, Lodish HF. An internal signal sequence: the asialoglycoprotein receptor membrane anchor. Cell 1986 Jan 17;44(1): 177-85.
[19] Spiess M, Handschin C. Deletion analysis of the internal signal-anchor domain of the human asialoglycoprotein receptor H1. EMBO J 1987 Sep;6(9):2683-91.
[20] Weigel PH, Yik JH. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta 2002 Sep 19;1572(2-3):341-63.
[21] Weigel PH. Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors. Bioessays 1994 Jul; 16(7):519-24.
[22] Becker S, Spiess M, Klenk HD. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol 1995 Feb;76 ( Pt 2):393-9.
[23]Treichel U, Meyer zum Buschenfelde KH, Dienes HP, Gerken G. Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol 1997;142(3):493-8.
[24]Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD. Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 2003 Jan;77(1):546-59.
[25]Dotzauer A, Gebhardt U, Bieback K, Gottke U, Kracke A, Mages J, et al. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol 2000 Dec;74(23): 10950-7.
[26]McFarlane BM, McSorley CG, Vergani D, McFarlane IG, Williams R. Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. J Hepatol 1986;3(2): 196-205.
[27]Treichel U, Poralla T, Hess G, Manns M, Meyer zum Biischenfelde KH. Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology 1990 Apr;11(4):606-12.
[28]Treichel U, Gerken G, Rossol S, Rotthauwe HW, Meyer zum Buschenfelde KH, Poralla T. Autoantibodies against the human asialoglycoprotein receptor: effects of therapy in autoimmune and virus-induced chronic active hepatitis. J Hepatol 1993 Aug;19(1):55-63.
[29]Hilgard P, Schreiter T, Stockert RJ, Gerken G, Treichel U. Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis. Hepatology 2004 May;39(5): 1398-407.
[1] Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 1990;249(4968):505-10.
[2] Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands.Nature 1990;346(6287):818-22.
[3] Brody EN, Gold L. Aptamers as therapeutic and diagnostic agents, J. Biotechnol 2000;74(1):5-13.
[4] Hicke BJ, Stephens AW. Escort aptamers: a delivery service for diagnosis and therapy. J.Clin. Invest 2000;106(8):923-8.
[5] Jayasena SD. Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin. Chem 1999;45(9): 1628-50.
[6] Geffen I., Spiess M. Asialoglycoprotein receptor. Int Rev Cytol 1992; 137B:181-219.
[7] Spiess M. The asialoglycoprotein receptor: a model for endocytic transport receptors.Biochemistry 1990;29(43): 10009-18.
[8] Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem.1985;260(4): 1979-82.
[9] Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A.1985;82(19):6465-9.
[10]Rhodes A, Deakin A, Spaull J, Coomber B, Aitken A, Life P, Rees S. The generation and characterization of antagonist RNA aptamers to human oncostatin M. J Biol Chem. 2000 Sep 15;275(37):28555-61.
[11]Pagratis NC, Bell C, Chang YF, Jennings S, Fitzwater T, Jellinek D, Dang C. Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor. Nat Biotechnol. 1997 Jan;15(1):68-73.
[12]Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA. RNA aptamers as reversible antagonists of coagulation factor IXa. Nature. 2002 Sep 5;419(6902):90-4.
[13] Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ. Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature. 1992 Feb 6;355(6360):564-6.
[14] Wiegand TW, Williams PB, Dreskin SC, Jouvin MH, Kinet JP, Tasset D. High-affinity oligonucleotide ligands to human IgE inhibit binding to Fc epsilon receptor I. J Immunol.1996 Jul 1;157(1):221-30.
[15] Watson SR, Chang YF, O'Connell D, Weigand L, Ringquist S, Parma DH. Anti-L-selectin aptamers: binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo. Antisense Nucleic Acid Drug Dev. 2000 Apr;10(2):63-75.
[16] Chapman JA, Beckey C. Pegaptanib: A novel approach to ocular neovascularization. Ann Pharmacother. 2006 Jul-Aug;40(7-8): 1322-6.
[17]Ng EW, Shima DT, Calias P, Cunningham ET Jr, Guyer DR, Adamis AP. Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease. Nat Rev Drug Discov. 2006 Feb;5(2): 123-32.
[18]McNamara JO 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH. Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol. 2006 Aug;24(8):1005-15.
[19]Chu TC, Twu KY, Ellington AD, Levy M. Aptamer mediated siRNA delivery. Nucleic Acids Res. 2006 Jun l;34(10):e73.
[20] Weigel PH, Yik JH. Glycans as endocytosis signals: the cases of the asialoglycoprotein and hyaluronan/chondroitin sulfate receptors. Biochim Biophys Acta. 2002 Sep 19;1572(2-3):341-63.
[1]Weigel PH,Yik JH.Glycans as endocytosis signals:the cases of the asialoglyco-protein and hyaluronan/chondroitin sulfate receptors.Biochim Biophys Acta.2002 Sep 19;1572(2-3):341-63.
[2]Geuze HJ,Slot JW,Strous GJ,Lodish HF,Schwartz AL.Intracellular site of asialoglycoprotein receptor-ligand uncoupling:double-label immunoelectron microscopy during receptor-mediated endocytosis.Cell 1983 Jan;32(1):277-87.
[3]Geuze HJ,Slot JW,Strous GJ,Peppard J,von Figura K,Hasilik A,Schwartz AL.Intracellular receptor sorting during endocytosis:comparative immunoelectron microscopy of multiple receptors in rat liver.Cell 1984 May;37(1):195-204.
[4]Geffen I.,Spiess M.Asialoglycoprotein receptor.Int Rev Cytol.1992;137B:181-219.
[5]Spiess M.The asialoglycoprotein receptor:a model for endocytic transport receptors.Biochemistry 1990 Oct 30;29(43):10009-18.
[6]Ashwell G.,Harford J.Carbohydrate-specific receptors of the liver.Ann.Rev.Biochem.1982;51:531-54.
[7]Stockert RJ,Morell AG..Hepatic binding protein:the galactose-specific receptor of mammalian hepatocytes. Hepatology, 1983 Sep-Oct;3(5):750-7.
[8] Ashwell G, Morell AG. The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv. Enzymol. 1974;41(0):99-128.
[9] Weigel PH, Schmell E, Lee YC, Roseman S. Specific adhesion of rat hepatocytes to beta-galactosides linked to polyacrylamide gels. J Biol Chem. (1978) 1978 Jan 25;253 (2):330-3.
[10]Schnaar RL, Weigel PH, Kuhlenschmidt MS, Lee YC, Roseman S. Adhesion of chicken hepatocytes to polyacrylamide gels derivatized with N-acetylglucosamine. J Biol Chem.1978 Nov 10;253(21):7940-51.
[11]Baenziger JU, Maynard Y. Human hepatic lectin: Physiochemical properties and specificity. J Biol Chem. 1980 May 25;255(10):4607-13.
[12]Ciechanover A, Schwartz AL, Lodish HF, Sorting and recycling of cell surface receptors and endocytosed ligands: the C and transferrin receptors, J Cell Biochem.1983;23(1-4):107-30.
[13]Abdullah M, Widgren EE, O'Rand MG. A mammalian sperm lectin related to rat hepatocyte lectin-2/3. Purification from rabbit testis and identification as a zona binding protein. Mol. Cell. Biochem. 1991 May 15;103(2):155-61.
[14]Goluboff ET, Mertz JR, Tres LL, Kierszenbaum AL. Galactosyl receptor in human testis and sperm is antigenically related to the minor C-type (Ca(2+)-dependent) lectin variant of human and rat liver. Mol Reprod Dev. 1995 Apr;40(4):460-6.
[15]Pacifico F, Liguoro D, Acquaviva R, Formisano S, Consiglio E. Thyroglobulin binding and TSH regulation of the RHL-1 subunit of the asialoglycoprotein receptor in rat thyroid. Biochimie. 1999May;81(5):493-6.
[16]Kolb-Bachofen V, Schlepper-Sch(a|¨)fer J, Vogell W, Kolb H. Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis. Cell. 1982 Jul;29(3):859-66.
[17]Ii M, Kurata H, Itoh N, Yamashina I, Kawasaki T. Molecular cloning and sequence analysis of cDNA encoding the macrophage lectin specific for galactose and N-acetylgalactosamine. J Biol Chem. 1990 Jul 5;265(19):11295-8.
[18]Mu JZ, Fallon RJ, Swanson PE, Carroll SB, Danaher M, Alpers DH. Expression of an endogenous asialoglycoprotein receptor in a human intestinal epithelial cell line, Caco-2, Biochim. Biophys. Acta 1994 Jul 21;1222(3):483-91.
[19]Valladeau J, Duvert-Frances V, Pin JJ. Kleijmeer MJ. Ait-Yahia S, Ravel O, Vincent C,Vega F Jr, Helms A, Gorman D. Zurawski SM, Zurawski G, Ford J, Saeland S. Immature human dendritic cells express asialoglycoprotein receptor isoforms for efficient receptor-mediated endocytosis. J Immunol. 2001 Nov 15; 167(10):5767-74.
[20]Seow YY, Tan MG, Woo KT. Expression of a functional asialoglycoprotein receptor in human renal proximal tubular epithelial cells. Nephron. 2002 Jul;91(3):431-8.
[21] Schwartz AL. The hepatic asialoglycoprotein receptor. CRC Crit. Rev. Biochem.1984;16(3):207-33.
[22]Breitfeld PP, Simmons CF Jr, Strous GJ, Geuze HJ, Schwartz AL. Cell biology of the asialoglycoprotein receptor system: a model of receptor-mediated endocytosis. Int Rev Cytol. 1985;97:47-95.
[23]Kawasaki T, Ashwell G. Carbohydrate structure of glycopeptides isolated from an hepatic membrane-binding protein specific for asialoglycoproteins, J. Biol. Chem. 1976 Sep 10;251(17):5292-9.
[24]Sanford JP, Doyle D. Mouse asialoglycoprotein receptor cDNA sequence: conservation of receptor genes during mammalian evolution. Biochim Biophys Acta. 1990 Oct 23;1087(2):259-61.
[25]Takezawa R, Shinzawa K, Watanabe Y, Akaike T. Determination of mouse major asialoglycoprotein receptor cDNA sequence. Biochim Biophys Acta. 1993 Feb 20;1172(l-2):220-2.
[26]Spiess M, Schwartz AL, Lodish HF. Sequence of human asialoglycoprotein receptor cDNA, an internal signal sequence for membrane insertion. J Biol Chem. 1985 Feb 25;260(4):1979-82.
[27]Spiess M, Lodish HF. Sequence of a second human asialoglycoprotein receptor: conservation of two receptor genes during evolution, Proc Natl Acad Sci U S A. 1985 Oct;82(19):6465-9.
[28]Drickamer K, Mamon JF, Binns G, Leung JO. Primary structure of the rat liver asialoglycoprotein receptor. Structural evidence for multiple polypeptide species, J Biol Chem. 1984 Jan 25;259(2):770-8. [29]Herzig MC, Weigel PH. Surface and internal galactosyl receptors are heterooligomers and retain this structure after ligand internalization or receptor modulation. Biochemistry.1990 Jul 10;29(27):6437-47.
[30]Paietta E, Stockert RJ, Racevskis J. Differences in the abundance of variably spliced transcripts for the second asialoglycoprotein receptor polypeptide, H2, in normal and transformed human liver, Hepatology. 1992 Mar;15(3):395-402.
[31]Yik JH, Saxena A, Weigel PH. The minor subunit splice variants, H2b and H2c, of the human asialoglycoprotein receptor are present with the major subunit H1 in different hetero-ligomeric receptor complexes. J Biol Chem. 2002 Jun 21;277(25):23076-83. Epub 2002 Apr 9.
[32]Tolchinsky S, Yuk MH, Ayalon M, Lodish HF, Lederkremer GZ. Membrane-bound versus secreted forms of human asialoglycoprotein receptor subunits: Role of a juxtamembrane pentapeptide. J Biol Chem. 1996 Jun 14;271(24):14496-503.
[33]Yago H, Kohgo Y, Kato J, Watanabe N, Sakamaki S, Niitsu Y. Detection and quantification of soluble asialoglycoprotein receptor in human serum. Hepatology. 1995 Feb;21(2):383-8.
[34]Chiacchia KB, Drickamer K. Direct evidence for the transmembrane orientation of the hepatic glycoprotein receptors. J Biol Chem. 1984 Dec 25;259(24): 15440-6.
[35]Fuhrer C, Geffen I, Huggel K, Spiess M. The two subunits of the asialoglycoprotein receptor contain different sorting information. J Biol Chem. 1994 Feb 4;269(5):3277-82.
[36]Bider MD, Wahlberg JM, Kammerer RA, Spiess M. The oligomerization domain of the asialoglycoprotein receptor preferentially forms 2:2 heterotetramers in vitro. J Biol Chem. 1996 Dec 13;271 (50):31996-2001.
[37] Meier M, Bider MD, Malashkevich VN, Spiess M, Burkhard P. Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. J Mol Biol. 2000 Jul 21;300(4):857-65.
[38]Hardy MR, Townsend RR, Parkhurst SM, Lee YC. Different modes of ligand binding to the hepatic galactose/N-acetylgalactosamine lectin on the surface of rabbit hepatocytes.Biochemistry. 1985 Jan 1;24(1):22-8.
[39] Oka JA, Herzig MC, Weigel PH. Functional galactosyl receptors on isolated rat hepatocytes are hetero-oligomers. Biochem Biophys Res Commun. 1990 Aug 16;170(3):1308-13.
[40]Braiterman LT, Chance SC, Porter WR. Lee YC, Townsend RR, Hubbard AL. The major subunit of the rat asialoglycoprotein receptor can function alone as a receptor. J Biol Chem. 1989 Jan 25;264(3):1682-8.
[41]Halberg DF, Wager RE, Farrell DC, Hildreth J 4th, Quesenberry MS, Loeb JA, Holland EC, Drickamer K. Major and minor forms of the rat liver asialoglycoprotein receptor are independent galactose-binding proteins. Primary structure and glycosylation heterogeneity of minor receptor forms. J Biol Chem. 1987 Jul 15;262(20):9828-38.
[42]Bider MD, Cescato R, Jeno P, Spiess M. High-affinity ligand binding to subunit H1 of the asialoglycoprotein receptor in the absence of subunit H2. Eur J Biochem. 1995 May 15;230(1):207-12.
[43]Saxena A, Yik JH, Weigel PH. H2, the minor subunit of the human asialoglycoprotein receptor, trafficks intracellularly and forms homo-oligomers, but does not bind asialo-orosomucoid. J Biol Chem. 2002 Sep 20;277(38):35297-304. Epub 2002 Jun 27.
[44] Collins JC, Stockert RJ, Morell AG. Asialoglycoprotein receptor expression in murine pregnancy and development. Hepatology, 1984 Jan-Feb;4(l):80-3.
[45]Petell JK, Doyle D. Developmental regulation of the hepatocyte receptor for galactose-terminated glycoproteins. Arch Biochem Biophys. 1985 Sep;241(2):550-60.
[46]Collins JC, Paietta E, Green R, Morell AG, Stockert RJ. Biotin-dependent expression of the asialoglycoprotein receptor in HepG2. J Biol Chem. 1988 Aug 15;263(23):11280-3.
[47] Stockert RJ. The asialoglycoprotein receptor: relationships between structure, function,and expression. Physiol Rev. 1995 Jul;75(3):591-609.
[48]Braun JR, Willnow TE, Ishibashi S, Ashwell G, Herz J. The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit. J Biol Chem. 1996 Aug 30;271(35):21160-6.
[49]Tozawa R, Ishibashi S, Osuga J, Yamamoto K, Yagyu H, Ohashi K, Tamura Y, Yahagi N, Iizuka Y, Okazaki H, Harada K, Gotoda T, Shimano H, Kimura S, Nagai R, Yamada N.Asialoglycoprotein receptor deficiency in mice lacking the major receptor subunit. Its obligate requirement for the stable expression of oligomeric receptor. J Biol Chem. 2001 Apr 20;276( 16): 12624-8. Epub 2001 Jan 16.
[50] Windier E, Greeve J, Levkau B, Kolb-Bachofen V, Daerr W, Greten H. The human asialoglycoprotein receptor is a possible binding site for low-density lipoproteins and chylomicron remnants. Biochem J. 1991 May 15;276 (Pt 1):79-87.
[51]Rotundo RF, Rebres RA, Mckeown-Longo PJ, Blumenstock FA, Saba TM. Circulating cellular fibronectin may be a natural ligand for the hepatic asialoglycoprotein receptor:possible pathway for fibronectin deposition and turnover in the rat liver. Hepatology. 1998 Aug;28(2):475-85.
[52]Weigel PH. Galactosyl and N-acetylgalactosaminyl homeostasis: a function for mammalian asialoglycoprotein receptors. BioEssays. 1994 Jul;16(7):519-24.
[53] Becker S, Spiess M, Klenk HD. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol. 1995 Feb;76 ( Pt 2):393-9.
[54]Treichel U, Meyer zum Buschenfelde KH, Dienes HP, Gerken G. Receptor-mediated entry of hepatitis B virus particles into liver cells. Arch Virol. 1997;142(3):493-8.
[55]Saunier B, Triyatni M, Ulianich L, Maruvada P, Yen P, Kohn LD. Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol. 2003 Jan;77(1):546-59.
[56]Dotzauer A, Gebhardt U, Bieback K, Gottke U, Kracke A, Mages J, Lemon SM, Vallbracht A. Hepatitis A virus-specific immunoglobulin A mediates infection of hepatocytes with hepatitis A virus via the asialoglycoprotein receptor. J Virol. 2000 Dec;74(23): 10950-7.
[57]U. Treichel , T. Poralla , G. Hess , M. Manns , K.H. Meyer zum Buschenfelde .Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis. Hepatology. (1990) Apr;11(4):606-12.
[58]Treichel U, Poralla T, Hess G, Manns M, Meyer zum Buschenfelde KH.Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis.Hepatology. 1990 Apr;11(4):606-12.
[59]Dizhe EB, Akifiev BN, Missul BV, Orlov SV, Kidgotko OV, Sukonina VE, Denisenko AD, Perevozchikov AP. Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo. Biochemistry (Mosc). 2001 Jan;66(1):55-61.
[60]Wang S, Cheng L, Yu F, Pan W, Zhang J. Delivery of different length poly(L-lysine)-conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects. Int J Pharm. 2006 Mar 27;311(1-2):82-8. Epub 2006 Jan 19.
[61] Peng DJ, Sun J, Wang YZ, Tian J, Zhang YH, Noteborn MH, Qu S. Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor. Cancer Gene Ther. 2007 Jan;14(1):66-73. Epub 2006 Jul 28.
[62] Di Stefano G, Kratz F, Lanza M, Fiume L. Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier. Dig Liver Dis. 2003 Jun;35(6):428-33.
[63] Di Stefano G, Fiume L, Domenicali M, Busi C, Chieco P, Kratz F, Lanza M, Mattioli A,Pariali M, Bernardi M. Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis. Dig Liver Dis. 2006 Jun;38(6):404-8. Epub 2006 Apr 3.
[64] Fiume L, Di Stefano G, Busi C, Mattioli A, Battista Gervasi G, Bertini M, Bartoli C,Catalani R, Caccia G, Farina C, Fissi A, Pieroni O, Giuseppetti R, D'Ugo E, Bruni R,Rapicetta M. Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate. J Hepatol. 1997 Feb;26(2):253-9.
[65] Yang J, Bo XC, Ding XR, Dai JM, Zhang ML, Wang XH, Wang SQ. Antisense oligonucleotides targeted against asialoglycoprotein receptor 1 block human hepatitis B virus replication. J Viral Hepat. 2006 Mar; 13(3): 158-65.
[66]Nomura Y, Yamasaki K, Sakamoto S, Hayasi N, Hosaka K, Fukusima K, Sugimura K,Sakai H, Nagai H. A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model. Kaku Igaku. 2000 Nov;37(6):631-8.
[1]Kao JH,Chen DS.Global control of hepatitis B virus infection.Lancet Infect Dis,2002;2:395-403.
[2]Parkin DM,Bray F,Ferlay J,Pisani P.Estimating the world cancer burden:Globocan 2000.Int J Cancer.2001;94(2):153-6.
[3]Ashwell G.,Morell AG..The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins.Adv.Enzymol.1974;41(0):99-128.
[4]Nishikawa M,Miyazaki C.Yamashita F,Takakura Y,Hashida M.Galactosylated proteins are recognized by the liver according to the surface density of galactose moieties.Am J Physiol.1995 May;268(5 Pt 1):G849-56.
[5]蔡春,苏敏,杨健,等.肝靶向前药半乳糖化人血清白蛋白氟尿嘧啶偶联物的合成及靶向作用.中国药学杂志,2006,41(10):786-789.
[6]Di Stefano G,Kratz F,Lanza M,Fiume L.Doxorubicin coupled to lactosaminated human albumin remains confined within mouse liver cells after the intracellular release from the carrier.Dig Liver Dis.2003 Jun;35(6):428-33.
[7]Di Stefano G,Fiume L,Domenicali M,Busi C,Chieco P,Kratz F,Lanza M,Mattioli A,Pariali M,Bernardi M.Doxorubicin coupled to lactosaminated albumin:Effects on rats with liver fibrosis and cirrhosis.Dig Liver Dis.2006 Jun;38(6):404-8.Epub 2006 Apt 3.
[8]Nomura Y,Yamasaki K,Sakamoto S,Hayasi N,Hosaka K,Fukusima K,Sugimura K,Sakai H,Nagai H.A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model.Kaku Igaku.2000 Nov;37(6):631-8.
[9]钟森,温守明,张定凤,等.乳糖化多聚赖氨酸导向反义寡核苷酸抗乙型肝炎病毒的作用.中华实验和临床病毒学杂志,2001,15(2):150-153.
[10]Dizhe EB,Akifiev BN,Missul BV,Orlov SV,Kidgotko OV,Sukonina VE,Denisenko AD,Perevozchikov AP.Receptor-mediated transfer of DNA-galactosylated poly-L-lysine complexes into mammalian cells in vitro and in vivo.Biochemistry(Mosc).2001 Jan;66(1):55-61.
[11]Wang S,Cheng L,Yu F,Pan W,Zhang J.Delivery,of different length poly(L-lysine)conjugated ODN to HepG2 cells using N-stearyllactobionamide-modified liposomes and their enhanced cellular biological effects.Int J Pharm.2006 Mar 27;311(1-2):82-8.Epub 2006Jan 19.
[12]Peng DJ,Sun J,Wang YZ,Tian J,Zhang YH,Notebom MH,Qu S.Inhibition of hepatocarcinoma by systemic delivery of Apoptin gene via the hepatic asialoglycoprotein receptor.Cancer Gene Ther.2007 Jan;14(1):66-73.Epub 2006 Jul 28.
[]3]王学东,冯永堂,陈相英,等.乳糖化赖氨酸与反义X基因质粒复合物体外对HBV表达的抑制.中国生化药物杂志,2005,26(4):205-207.
[14]Fiume L,Di Stefano G,Busi C,Mattioli A,Battista Gervasi G,Bertini M,Bartoli C,Catalani R,Caccia G,Farina C,Fissi A,Pieroni O,Giuseppetti R,D'Ugo E,Bruni R,Rapicetta M.Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine.Synthesis of the carrier and pharmacological properties of the conjugate.J Hepatol.1997 Feb;26(2):253-9.
[15]Hashida M,Hirabayashi H,Nishikawa M,Takakura Y..Targeted delivery of drugs and proteins to the liver via receptor-mediated endocytosis.J Controlled Release,1997,46(1-2):129-137.
[16]Gao S,Chen J,Dong L,Ding Z,Yang YH,Zhang J.Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector.Eur J Pharm Biopharm.2005 Aug;60(3):327-34.
[17]Mi FL,Yu SH,Peng CK,et al.Synthesis and characterization of a novel glycoconjugated macromolecule.Polymer,2006,47(12):4348-4358.
[]8]黄容琴,裴元英.主动肿瘤靶向给药系统的研究进展.中国医药工业杂志,2005,36(8):505-510.
[19]侯新朴,王黎,王向涛,等.脂质体肝实质细胞靶向性研究.药学学报,2003,38(2):143-146.
[20]Biessen EA,Bakkeren HF,Beuting DM,Kuiper J,Van Berkel TJ.Ligand size is a major determinant of high-affinity binding of fucose-and galactose-exposing(lipo)proteins by the hepatic fucose receptor.Biochem J,1994,299(Pt 1):291-296.
[21]Higuchi Y,Nishikawa M,Kawakami S,Yamashita E Hashida M.Uptake characteristics of mannosylated and fucosylated bovine serum albumin in primary cultured rat sinusoidal endothelial cells and Kupffer cells.In J Pharm,2004,287(1-2):147-154.
[22]Weiss SI,Sieverling N,Niclasen M,Maucksch C,Th(u|¨)nemann AE M6hwald H,Reinhardt D,Rosenecker J,Rudolph C.Uronic acids functionalized polyethyleneimine (PEI)-polyethyleneglycol(PEG)-grafl-copolymers as novel synthetic gene carriers.Biomaterials,2006,27(10):2302-2312.
[23]Opanasopit P,Sakai M,Nishikawa M,Kawakami S,Yarnashita E Hashida M.Inhibition of liver metastasis by targeting of irnmunomodulators using mannosylated liposome carriers.J Controlled Release,2002,80(1-3):283-294.
[24]Dierling AM,Cui ZR.Targeting primaquine into liver using chylomicron emulsions for potential vivax malaria therapy.Int J Pharm,2005,303(1-2):143-152.
[25]Jansen RW,Molema G,Harms G,Kruijt JK,van Berkel YJ,Hardonk MJ,Meijer DK.Formaldehyde treated albumin contains monomeric and polymeric forms that are differently cleared by endothelial and Kupffer cells of the liver:evidence for scavenger receptor heterogeneity.Biochem Biophys Res Commun,1991,180(1):23-32.
[26]Furitsu H,Ogawara K,Fujita T,et al.Pharmacokinetic analysis of scavenger receptor-mediated uptake of anionized proteins in the isolated perfused rat liver.Int J Pharm,1997,151(1):15-26.
[27]高 艳,李厚丽,吕青志,翟光喜.主动转运途径在肝靶向给药系统中的应用.中国医药工业杂志,2008,39(7):542-547.
[28]Beljaars L,Molema G,Weert B,Bonnema H,Olinga P,Groothuis GM,Meijer DK,Poelstra K.Albumin Modified With Mannose 6-Phosphate:A Potential Carrier for Selective Delivery of Antifibrotic Drugs to Rat and Human Hepatic Stellate Cells.Hepatology,1999,29(5):1486-1493.
[29]张其胜,Luk JM,张健,等.甘草次酸靶向肝星状细胞治疗肝纤维化的体内研究。中华肝脏病杂志,2005,13(9):664-667.
[30]Greupink R,Bakker HI,Reker-Smit C,van Loenen-Weemaes AM,Kok RJ,Meijer DK, Beljaars L,Poelstra K.Studies on the targeted delivery,of the antifibrogenic compound mycophenolic acid to the hepatic stellate cell.J Hepatol,2005,43(5):884-892.
[31]Adrian JE,Kamps JA,Scherphof GL,Meijer DK,van Loenen-Weemaes AM,Reker-Smit C,Terpstra P,Poelstra K.A novel lipidbased drug carrier targeted to the non-parenchymal cells,including hepatic stellate cells,in the fibrotic livers of bile duct ligated rats.Biochim BiophyActa,2007,1768(6):1430-1439.
[32]杜施霖,王吉耀,潘弘,等.含有RGD序列环肽介导的干扰素脂质体对大鼠肝纤维化的治疗作用.中华医学杂志,2005,85(15):1015-1020.
[33]Nada H,Wu CH,Wu GY.Chemical modifi-canon of an ecotropic marine leukemia virus results in redirection of its target cell speci-ficity.J Biol Chem,1991,266;14143-14146.
[34]Cristiano W,Smith LC,Woo SI.Hepatic gene therapy;adenovirus enhancement of receptomediated gene delivery and expression in ptvrtaty hepatocytes.Proc Natl Acad Sci USA,1993,90:2122-2126.
[35]Kaneda Y,Saeki Y,Morishita R.Gene therapy using HVJIiposomes:the best of both worlds? Mol Med Today,1999.5(7):298-303
[36]Limuro Y,Fujimoto J.Strategy of gene therapy for liver cirrhosis and hepatocellular carcinoma.J Hepatobiliary Pancreat Surg,2003,10(1):45-47.
[37]Hazra B,Pore V,Dey S,Datta S,Darokar M,Saikia D,Khanuja SP,Thakur A.Bile acid amides derived from chiral amino alcohols:novel antimicrobials and antifungals.Bioorg Med Chem Lett,2004,14(3):773-777.
[38]Tu N,Link JT,Sorensen BK,Emery M,Grynfarb M.Goos-Nilsson A,Nguyen B.Bile acid conjugates of a nonsteroidal glucocorticoid receptor modulator.Bioorg Med Chem Lett,2004,14(16):4179-4183.
[39]Fiorucci S,Antonelli E,Brancaleone V,Sanpaolo L,Orlandi S,Distrutti E,Acuto G,Clerici C,Baldoni M,Del Soldato P,Morelli A.NCX-1000,a nitric oxide-releasing derivative of ursodeoxycholic acid,ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver.J Hepatol,2003,39(6):932-939.
[40]陈莉,蒋丽媛,张奕华.NCX-1000的新合成方法.药学进展,2003,27(6):358-360.
[41]Erion MD,van Poelje PD,Mackenna DA,Colby TJ,Montag AC,Fujitaki JM,Linemeyer DL, Bullough DA. Liver Targeted Drug Delivery Using HepDirectl Prodrugs. J Pharmacol Exp Then 2005, 312 (2): 554-560.
[42] Lin CC, Fang C, Benetton S, Xu GF, Yeh LT. Metabolic activation of pradefovir by CYP3A4 and its potential as an inhibitor or inducer. Antimicrob Agents Chemother, 2006,50 (9): 2926-2931.
[43]Liu F, Song Y, Liu D. Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Then 1999, 6 (7): 1258-1266.
[44] Zhang G, Song YK, Liu D. Long-term expression DNA using a hydrodynamics-based procedure. Gene Ther, 2000,7 (15): 1344-1349.
[45]Kobayashi N, Kuramoto I, Yamaoka K, Hashida M, Takakura Y. Hepatic Uptake and Gene Expression Mechanisms following Intravenous Administration of Plasmid DNA by Conventional and Hydrodynamics-Based Procedures. J Pharmacol Exp Ther, 2001,297(3): 853-860.