PSI诱导的PC12细胞PD模型中硝化、磷酸化和糖基化亚蛋白质组的研究
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摘要
目的研究PSI处理后PC12细胞的硝化、磷酸化和糖基化亚蛋白质组的变化,筛选出新的与PD、UPS相关的被异常修饰的蛋白,为PD的病因病理和临床治疗研究提供新的思路。方法建立PSI诱导的PC12细胞PD模型,提取细胞总蛋白,分别采用1)双向电泳、Western blot与质谱相结合的硝化亚蛋白质组学技术,2)双向电泳、Pro-Q Diamand磷酸化蛋白凝胶染色与质谱相结合的磷酸化亚蛋白质组学技术,3)双向电泳、Pro-Q Emerald 488糖基化蛋白凝胶染色与质谱相结合的糖基化亚蛋白质组学技术,获得差异蛋白点,并鉴定出差异蛋白。结果PSI处理后PC12细胞凋亡百分比为10%,大约在80%的细胞中诱导出包涵体;12个蛋白点的相对硝化水平发生显著改变,CCT 6a、lamin A、p60 protein和G3BP显著升高;24个蛋白点Pro-Q Diamand染色强度发生显著改变,分别为上调的TH、peripherin、p47和HSP27,以及下调的NPM和AR,同时TH、peripherin和HSP27的相对磷酸化水平显著升高,p47、NPM和AR的相对磷酸化水平显著下降;12个蛋白点Pro-Q Emerald 488染色强度发生显著改变,分别为上调的ORP150和annexin II,以及下调的p-ALDH,ORP150的相对糖基化水平显著升高,p-ALDH的相对糖基化水平显著下降,annexin II的相对糖基化水平无变化。讨论本研究成功地建立了蛋白酶体抑制的PD细胞模型,比较蛋白的硝化、磷酸化和糖基化水平的变化,分别探讨差异蛋白及其相关异常修饰在PD及PSI诱导的PC12细胞PD模型中可能的作用。本研究发现的CCT 6a、p60、lamin A、G3BP蛋白及其硝化修饰,p47、AR和NPM蛋白及其磷酸化修饰,annexin II蛋白及其糖基化修饰在以往关于PD的研究中均未被报道过,本研究也首次发现磷酸化的TH和HSP27、糖基化的ORP150和p-ALDH在蛋白酶体受到抑制后发生显著变化。这些发现为进一步阐明PD的发病机制和寻求PD药物治疗靶点提供了新的线索。
Parkinson disease (PD) is a slowly progressive age-related neurodegenerative disorder that can be familial or sporadic, characterized with the preferential degeneration and loss of dopaminergic neuron of the substantia nigra pars compacta and the presence of Lewy body in the survival neurons. The etiology and etiopathogenesis of PD are still obscure, recent studies suggest that defects in the capacity of the ubiquitin-proteasome system (UPS) to degrade unwanted proteins may be a common feature in both of familial and sporadic forms of PD. The cell and animal models induced by proteasome inhibitors have been successfully established, which could be the closest model of PD so far.
Nitration, phosphorylation and glycosylation of proteins are the important post-translation modifications (PTMs), and recent studies show that the abnormal modifications may play a key role in the etiopathogenesis and pathological process of PD. At present the researches of damages caused by abnormal PTMs in PD are carried out at single protein level, which depend on the precise hypothesis of proteins assumed to be modified and the attainment of antibody of the protein. The newly developed proteomic techniques of PTMs make it possible to find a batch of proteins that are modified in one experiment, so many abnormal modifications of proteins will be found, which can’t be or haven’t been discovered with the traditional methods.
The aim of this study was to establish the PD model of PC12 cell with PSI, examine entirely the nitrated, phosphorylated and glycosylated proteins with the proteomic techniques of PTMs, analyze the impact of PSI on protein modifications, and find some new abnormally modified proteins which are related to PD and UPS.
The PC12 cells were cultured with routine methods, then respectively exposed to DMSO (in the control group) and PSI (in the experiment group,disolved in DMSO). After 24 hours PC12 cells were harvested and the total proteins were extracted. The differences of protein nitration between two groups were obtained by two-dimensional gel electrophoresis (2-DE), Western blot and Coomasie Blue stain. The differences of protein phosphorylation between two groups were obtained by 2-DE, Pro-Q Diamand phosphoprotein stain and Coomasie Blue stain. The differences of protein glycosylation between two groups were obtained by 2-DE, Pro-Q Emerald 488 glycoprotein stain and Coomasie Blue stain. Then certain proteins were identified by MALDI-TOF MS.
After exposed to PSI for 24 hours, 10% of PC12 cells were dead and cellular inclusions beside the nucleus were observed in 80% of the survival cells. The nitration of 12 protein spots were significantly changed, 4 of which were successfully identified by MALDI-TOF MS. They were chaperonin subunit 6a (CCT 6a), lamin A, p60 protein, and Ras-GTPase-activating protein SH3-domain binding protein (G3BP), the nitrations of which were increased significantlly. CCT and p60 are molecular-chaperone and molecular-chaperone cofactor, which involve in the cellular protein-quality control; lamin A is an intermediate filaments protein, participating in the construction of cytoskeleton; G3BP is a protein with endogenous ribonulease activity and ATP/Mg2+ dependent DNA/RNA helicase activity which binds to the SH3 domain of Ras-GTPase activating protein.
After exposed to PSI for 24 hours, the Pro-Q Diamand intensity of 24 proteins were significantly changed, 6 of which were identified by MALDI-TOF MS. The phosphoryaltion of tyrosine hydroxylase (TH), peripherin, p47, and heat shock protein 27 (HSP27) were increased, while the phosphorylations of nucleolar phosphoprotein B23 (NPM) and aldehyde reductase 1 (AR) were decreased. Then the relative phosphorylation of the above proteins were further analyzed, that of peripherin, HSP27 and TH were increased and p47, NPM and AR were decreased. TH is the rate-limiting enzyme of the biosynthesis of catecholamine and the biomarker of dopaminergic neurons, which catalyzes the conversion of L-tyrosine to DOPA; peripherin is a III-type intermediate filament protein which exclusively expresses in the neurons of peripheral nervous system (PNS), and in the neurons of CNS directly projecting to the periphery, the biological functions of which, especially in the brain, are still poorly understood; p47 is a cofactor of p97 (a AAA-ATPase), which binds to p97 and participates in the memberane fusion of Golgi and endoplasmic reticulum (ER), as well as the degradation of a small subset of VCP-dependent UPS substrates; HSP27 belongs to the small heat shock proteins family (sHSP), main functions of which are to facilitate the folding of proteins and inhibit the aggregation of abnormal proteins; NPM is a nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm during the cell cycle and has several interacting partners and diverse cellular functions; AR belongs to the aldo-keto reductase superfamily, and catalyzes the conversion of aldehyde to acetic acid using NAD(P)(H) as a cofactor, that may have roles in glucose metabolism, aldehyde metabolism, and electron transport.
After exposed to PSI for 24 hours, the intensity of Pro-Q Emerald 488 stain of 12 proteins were significantly changed, 3 of which were identified by MALDI-TOF MS. The glycosylations of 150kDa oxgen-regulated protein precursor (ORP150) and annexin II were increased,while the glycosylation of mitochondrial aldehyde dehydrogenase precursor (p-ALDH) was decreased. Then the relative glycosylation of the above proteins were analyzed, that of ORP150 was increased, p-ALDH was decreased and annexin II was unchanged. ORP150 locates in ER and is an ER-associated glycoprotein with molecular-chaperone activity; annexin II is involved in the formation of Adherens Junctions, endocytosis, exocytosis, the maintenance of cytoskeleton and so on; p-ALDH locates in the mitochondria, and is involved in the oxidation of aldehydes derived from neurotransmitters and lipid peroxidation.
After searching on PubMed, we found that the nitrations and relative nitration levels of CCT 6a, p60, lamin A, G3BP, the phosphorylation and relative phosphorylation levels of p47, AR, NPM, the glycosylation and relative glycosylation level of annexin II, were not reported in previous studies of PD. Also, we first confirmed the changes of phosphorylated TH, HSP27 and their phosphorylation levels, glycosylated ORP150, p-ALDH and their glycosylation levels in PD model of PC12 treated with PSI. All these findings may provide new clues on the etiopathogenesis of PD and the targets of drug treatments.
Parkinson disease (PD) is a slowly progressive age-related neurodegenerative disorder that can be familial or sporadic, characterized with the preferential degeneration and loss of dopaminergic neuron of the substantia nigra pars compacta and the presence of Lewy body in the survival neurons. The etiology and etiopathogenesis of PD are still obscure, recent studies suggest that defects in the capacity of the ubiquitin-proteasome system (UPS) to degrade unwanted proteins may be a common feature in both of familial and sporadic forms of PD. The cell and animal models induced by proteasome inhibitors have been successfully established, which could be the closest model of PD so far.
Nitration, phosphorylation and glycosylation of proteins are the important post-translation modifications (PTMs), and recent studies show that the abnormal modifications may play a key role in the etiopathogenesis and pathological process of PD. At present the researches of damages caused by abnormal PTMs in PD are carried out at single protein level, which depend on the precise hypothesis of proteins assumed to be modified and the attainment of antibody of the protein. The newly developed proteomic techniques of PTMs make it possible to find a batch of proteins that are modified in one experiment, so many abnormal modifications of proteins will be found, which can’t be or haven’t been discovered with the traditional methods.
The aim of this study was to establish the PD model of PC12 cell with PSI, examine entirely the nitrated, phosphorylated and glycosylated proteins with the proteomic techniques of PTMs, analyze the impact of PSI on protein modifications, and find some new abnormally modified proteins which are related to PD and UPS.
The PC12 cells were cultured with routine methods, then respectively exposed to DMSO (in the control group) and PSI (in the experiment group,disolved in DMSO). After 24 hours PC12 cells were harvested and the total proteins were extracted. The differences of protein nitration between two groups were obtained by two-dimensional gel electrophoresis (2-DE), Western blot and Coomasie Blue stain. The differences of protein phosphorylation between two groups were obtained by 2-DE, Pro-Q Diamand phosphoprotein stain and Coomasie Blue stain. The differences of protein glycosylation between two groups were obtained by 2-DE, Pro-Q Emerald 488 glycoprotein stain and Coomasie Blue stain. Then certain proteins were identified by MALDI-TOF MS.
After exposed to PSI for 24 hours, 10% of PC12 cells were dead and cellular inclusions beside the nucleus were observed in 80% of the survival cells. The nitration of 12 protein spots were significantly changed, 4 of which were successfully identified by MALDI-TOF MS. They were chaperonin subunit 6a (CCT 6a), lamin A, p60 protein, and Ras-GTPase-activating protein SH3-domain binding protein (G3BP), the nitrations of which were increased significantlly. CCT and p60 are molecular-chaperone and molecular-chaperone cofactor, which involve in the cellular protein-quality control; lamin A is an intermediate filaments protein, participating in the construction of cytoskeleton; G3BP is a protein with endogenous ribonulease activity and ATP/Mg2+ dependent DNA/RNA helicase activity which binds to the SH3 domain of Ras-GTPase activating protein.
After exposed to PSI for 24 hours, the Pro-Q Diamand intensity of 24 proteins were significantly changed, 6 of which were identified by MALDI-TOF MS. The phosphoryaltion of tyrosine hydroxylase (TH), peripherin, p47, and heat shock protein 27 (HSP27) were increased, while the phosphorylations of nucleolar phosphoprotein B23 (NPM) and aldehyde reductase 1 (AR) were decreased. Then the relative phosphorylation of the above proteins were further analyzed, that of peripherin, HSP27 and TH were increased and p47, NPM and AR were decreased. TH is the rate-limiting enzyme of the biosynthesis of catecholamine and the biomarker of dopaminergic neurons, which catalyzes the conversion of L-tyrosine to DOPA; peripherin is a III-type intermediate filament protein which exclusively expresses in the neurons of peripheral nervous system (PNS), and in the neurons of CNS directly projecting to the periphery, the biological functions of which, especially in the brain, are still poorly understood; p47 is a cofactor of p97 (a AAA-ATPase), which binds to p97 and participates in the memberane fusion of Golgi and endoplasmic reticulum (ER), as well as the degradation of a small subset of VCP-dependent UPS substrates; HSP27 belongs to the small heat shock proteins family (sHSP), main functions of which are to facilitate the folding of proteins and inhibit the aggregation of abnormal proteins; NPM is a nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm during the cell cycle and has several interacting partners and diverse cellular functions; AR belongs to the aldo-keto reductase superfamily, and catalyzes the conversion of aldehyde to acetic acid using NAD(P)(H) as a cofactor, that may have roles in glucose metabolism, aldehyde metabolism, and electron transport.
After exposed to PSI for 24 hours, the intensity of Pro-Q Emerald 488 stain of 12 proteins were significantly changed, 3 of which were identified by MALDI-TOF MS. The glycosylations of 150kDa oxgen-regulated protein precursor (ORP150) and annexin II were increased,while the glycosylation of mitochondrial aldehyde dehydrogenase precursor (p-ALDH) was decreased. Then the relative glycosylation of the above proteins were analyzed, that of ORP150 was increased, p-ALDH was decreased and annexin II was unchanged. ORP150 locates in ER and is an ER-associated glycoprotein with molecular-chaperone activity; annexin II is involved in the formation of Adherens Junctions, endocytosis, exocytosis, the maintenance of cytoskeleton and so on; p-ALDH locates in the mitochondria, and is involved in the oxidation of aldehydes derived from neurotransmitters and lipid peroxidation.
After searching on PubMed, we found that the nitrations and relative nitration levels of CCT 6a, p60, lamin A, G3BP, the phosphorylation and relative phosphorylation levels of p47, AR, NPM, the glycosylation and relative glycosylation level of annexin II, were not reported in previous studies of PD. Also, we first confirmed the changes of phosphorylated TH, HSP27 and their phosphorylation levels, glycosylated ORP150, p-ALDH and their glycosylation levels in PD model of PC12 treated with PSI. All these findings may provide new clues on the etiopathogenesis of PD and the targets of drug treatments.
引文
1 McNaught KS, Olanow CW. Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson′s disease. Ann Neurol. 2003, 53(Suppl 3):73-86.
2 Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science. 2000, 290(5493): 985-989.
3 Przedborski S, Chen Q, Vila M, et al. Oxidative post-translational modifications of a-synuclein in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J Neurochem. 2001, 76(2): 637-640.
4 Aoyama K, Matsubara K, Fujikawa Y, et al. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol. 2000, 47(4):524-527.
5 Gatto EM, Riobo NA, Carreras MC, et al. Overexpression of neuronal nitric oxide synthase in Parkinson’s disease. Nitric oxide. 2000, 4(5):534-539.
6 Castegna A, Thongboonkerd V, Klein JB, et al. Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem. 2003, 85(6):1394-1401.
7 Maruyama Y, Teraoka H, Iwata H, et al. Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells. Neurochem Int. 2001, 38(7):567-572.
8 Wang JJ, Zhang T, Niu DB, et al. Doxycycline-regulated co-expression ofGDNF and TH in PC12 cells. Neurosci Lett. 2006, 401(1-2):142-145.
9 Wei Q, Yeung M, Jurma OP, et al. Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP. J Neurosci Res. 1996, 46(6):666-673.
10 Jha N, Kumar MJ, Boonplueang R, et al. Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin protein degradation pathway: relevance for Parkinson’s disease? J Neurochem. 2002, 80(4):555-561.
11 McNaught KS, Olanow CW, Halliwell B, et al. Failure of the ubiquitin-proteasome system in Parkinson’s disease. Nat Rev Neurosci. 2001, 2(8):589-594.
12 Rideout HJ, Larsen KE, Sulzer D, et al. Proteasomal inhibition leads to formation of ubiquitin / α-synuclein - immunoreactive inclusions in PC12 cells. J Neurochem. 2001, 78(4):899-908.
13 McNaught KS, Perl DP Brownell AL, et al. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Ann Neurol. 2004, 56(1):149-162.
14 Ross CA, Pickart CM. The ubiquitin-proteasome pathway in Parkinson’s disease and other neurodegenerative diseases. Trends Cell Biol. 2004, 14(12):703-711.
15 McNaught KS, Jackson T, JnoBaptiste R, et al. Proteasome dysfunction in sporadic Parkinson’s disease. Neurology. 2006, 66(10 Suppl 4):S37-S49.
16 Macario AJ, Grippo TM, de Macario EC. Genetic disorders involving molecular-chaperone genes: a perspective. Genet Med. 2005, 7(1):3-12.
17 张磊, 陈秋惠, 常明等. 蛋白质组学技术对 PC12 细胞热休克蛋白的鉴定.中国老年学杂志. 2006, 26(10):1400-1401.
18 Roobol A, Sahyoun ZP, Carden MJ. Selected subunits of the cytosolic chaperonin associate with microtubules assembled in vitro. J Biol Chem. 1999, 274(4):2408-2415.
19 Yokata S, Yanagi H, Yura T, et al. Cytosilic chaperonin-containing t-complex polypeptide 1 changes the content of a particular subunit species concomitant with substrate binding and folding activities during the cell cycle. Eur J Biochem. 2001, 268(17):4664-4673.
20 Shirvan A, Ziv I, Barzilai A, et al. Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons. J Neural Transm Suppl. 1997, 50:67-78.
21 Horiguchi R, Dohra H, Tokumoto T. Comparative proteome analysis of changes in the 26S proteasome during oocyte maturation in goldfish. Proteomics. 2006, 6(14):4195-4202.
22 Demand J, Lüders J, H?hfeld J. The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperon cofactors. Mol Cell Biol. 1998, 18(4):2023-2028.
23 张磊, 许忠, 常明等. 蛋白质组学技术鉴定的 PC12 细胞细胞骨架蛋白. 脑与神经疾病杂志. 2006, 14(3):190-192.
24 Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
25 Frasier M, Walzer M, McCarthy L, et al. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol. 2005,192(2):274-287.
26 Zastrow MS, Vlcek S, Wilson KL. Proteins that bind A-type lamins: integrating isolated clues. J Cell Sci. 2004, 117(7):979-987.
27 宁钧宇, 由江峰, 裴斐等. G3BP 单克隆抗体制备及 G3BP 在肿瘤组织中表达的检测. 2005, 34(4):215-219.
28 Grunblatt E, Mandel S, Jacob-Hirsch J, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm. 2004, 111(12):1543-1573.
29 Jullien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998, 61:1-23.
30 Brion JP, Couck AM. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Am J Pathol. 1995, 147(5):1465-1476.
31 Iwatsubo T, Nakano I, Fukunaga K, et al. Ca2+/calmodulin-dependent protein kinase II immunoreactivity in Lewy bodies. Acta Neuropathol (Berl). 1991, 82(3):159-163.
32 Okochi M, Walter J, Koyama A, et al. Constitutive phosphorylation of the Parkinson’s disease Associated α-synuclein. J Biol Chem. 2000, 275(1):390-397.
33 Iwatsubo T. Aggregation of α-synuclein in the pathogenesis of Parkinson’s disease. J Neurol. 2003, 250(Suppl 3): III/11-III/14.
34 Lee G, Tanaka M, Park K, et al. Casein kinase II-mediated phosphorylation regulates α-synuclein / synphilin-1 interaction and inclusion body formation.J Biol Chem. 2004, 279(8):6834-6839.
35 Wu DC, Teismann P, Tieu K, et al. NADPH oxidase mediates oxidative stress in the 1-methyl-4- phenyl - 1,2,3,6 - tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci USA. 2003, 100(10):6145-6150.
36 Steinberg TH, Agnew BJ, Gee KR, et al. Global quantitative phosphoprotein analysis using multiplexed proteomics technology. Proteomics. 2003, 3(7):1128-1144.
37 Yuan X, Simpson P, McKeown C, et al. Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97. EMBO J. 2004, 23(7):1463-1473.
38 Uchiyama K, Kondo H. p97/p47-mediated biogenesis of Golgi and ER. J Biochem (Tokyo). 2005, 137(2):115-119.
39 Kano F, Kondo H, Yamamoto A, et al. The maintenance of the endoplasmic reticulum network is regulated by p47, a cofactor of p97, through phosphorylation by cdc2 kinase. Genes Cells. 2005, 10(4):333-344.
40 Uchiyama K, Jokitalo E, Lindman M, et al. The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle. J Cell Biol. 2003, 161(6):1067-1079.
41 Hirabayashi M, Inoue K, Tanaka K, et al. VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration. Cell Death Differ. 2001, 8(10):977-984.
42 Wójcik C, Yano M, DeMartino GN. RNA interference of valosin-containing protein(VCP/p97) reveals multiple cellular roles linked to ubiquitin/proteasome-dependent proteolysis. J Cell Sci. 2004, 117 (2):281-292.
43 Nagahama M, Suzuki M, Hamada Y, et al. SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation. Mol Biol Cell. 2003, 14(1): 262-273.
44 Hartmann-Petersen R, Wallace M, Hofmann K, et al. The Ubx2 and Ubx3 cofactors direct Cdc48 activity to proteolytic and nonproteolytic ubiquitin-dependent processes. Curr Biol. 2004, 14(9):824-828.
45 Parcellier A, Schmitt E, Brunet M, et al. Small heat shock proteins HSP27 and αB-Crystallin: cytoprotective and oncogenic functions. Antioxid Redox Signal. 2005, 7(3-4):404-413.
46 Gorman AM, Szegezdi E, Quigney DJ, et al. Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells. Biochem Biophys Res Commnu. 2005, 327(3):801-810.
47 Ito H, Kamei K, Iwamoto I, et al. Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J Biochem. 2002, 131(4):593-603.
48 Fujisawa H, Okuno S. Regulatory mechanism of tyrosine hydroxylase activity. Biochem Biophys Res Commnu. 2005, 338(1):271-276.
49 Kaufman S. Tyrosine hydroxylase. Adv Enzymol Relat Areas Mol Biol. 1995,70:103-220.
50 Mori F, Nishie M, Kakita A, et al. Relationship among α-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J Neuropathol Exp Neurol. 2006, 65(8):808-815.
51 Chuenkova MV, Pereiraperrin M. Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi parasite-derived neurotrophic factor. Brain Res. 2006, 1099(1):167-175.
52 张克忠, 王坚, 蒋雨平. Lactacystin 对酪氨酸羟化酶基因和蛋白表达的影响. 中国临床神经科学. 2005, 13(2):144-148.
53 Hyndman D, Bauman DR, Heredia VV. The aldo-keto reductase superfamily homepage. Chem Biol Interac. 2003, 143-144:621-631.
54 Allan D, Lohnes D. Cloning and developmental expression of mouse aldehyde reductase (AKR1A4). Mech Dev. 2000, 94(1-2):271-275.
55 Davydov VV, Dobaeva NM, Bozhkov AI. Possible role of alteration of aldehyde’s scavenger enzymes during aging. Exp Gerontol. 2004, 39(1):11-16.
56 周丹, 倪晓华. 核磷蛋白的生物学功能及其与肿瘤发生的关系. 生命的化学. 2006, 26(3):244-247.
57 Lim MJ, Wang XW. Nucleophosmin and human cancer. Cancer Detect Prev. 2006, 30(6):481-490.
58 Xiao S, McLean J, Robertson J. Neuronal intermediate filaments and ALS: a new look at an old question. Biochim Biophys Acta. 2006, 1762(11-12):1001-1012.
59 Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci. 2005, 233(1-2):183-198.
60 Cairns NJ, Jaros E, Perry RH, et al. Temporal lobe pathology of human patients with neurofilament inclusion disease. Neurosci Lett. 2004, 354(3):245-247.
61 Kriz J, Beaulieu JM, Julien JP, et al. Up-regulation of peripherin is associated with alterations in synaptic plasticity in CA1 and CA3 regions of hippocampus. Neurobiol Dis. 2005, 18(2):409-420.
62 Huc C, Escurat M, Djabali K, et al. Phosphorylation of peripherin, anintermediate filament protein, in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons. Biochem Biophys Res Commnu. 1989, 160(2):772-779.
63 Goldknopf IL, Sheta EA, Bryson J, et al. Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem Biophys Res Commun. 2006, 342(4):1034-1039.
64 Kim YS, Lee SJ. Novel covalent modifications of alpha-synuclein during the recovery from proteasomal dysfunction. Biochem Biophys Res Commun. 2006, 346(4):1312-1319.
65 Wu J, Lenchik NJ, Pabst MJ, et al. Functional characterization of two-dimensional gel-separated proteins using sequential staining. Electrophoresis. 2005, 26(1):225-237.
66 Yu LG, Andrews N, Weldon M, et al. An N-terminal truncated form of Orp150 is a cytoplasmic ligand for the anti-proliferative mushroom Agaricus bisporus lectin and is required for nuclear localization sequence-dependent nuclear protein import. J Biol Chem. 2002, 277(27):24538-24545.
67 Kuwabara K, Matsumoto M, Ikeda J, et al. Purification and characterization of a novel stress protein, the 150-kDa oxygen-regulated protein(ORP150), from cultured rat astrocytes and its expression in ischemic mouse brain. The Journal of Biological Chemistry. 1996, 271(9):5025-5032.
68 Tohyama M, Ogawa T. Stress response of cultured astrocytes to hypoxia/reoxygenation. Nippon Yakurigaku Zasshi. 1997, 109(3):145-151.
69 Bando Y, Ogawa S, Yamauchi A, et al. 150-kDa oxygen-regulated protein(ORP150) functions as a novel molecular chaperone in MDCK cells. Am J Physiol Cell Physiol. 2000, 278(6):1172-1182.
70 Tsukamoto Y, Kuwabara K, Hirota S, et al. 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein. J Clin Invest. 1996, 98(8):1930-1941.
71 Ozawa K, Tsukamoto Y, Hori O, et al. Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone. Cancer Res. 2001, 61(10): 4206-4213.
72 Miyazaki M, Ozawa K, Hori O, et al. Expression of 150-kd oxygen-regulated protein in the hippocampus suppresses delayed neuronal cell death. J Cereb Blood Flow Metab. 2002, 22(8):979-987.
73 Kitao Y, Ozawa K, Miyazaki M, et al. Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity. J Clin Invest. 2001, 108(10):1439-1450.
74 Kobayashi T, Ohta Y. 150-kD oxygen-regulated protein is an essential factor for insulin release. Pancreas. 2005, 30(4):299-306.
75 Ozawa K, Miyazaki M, Matsuhisa M, et al. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes. 2005, 54(3):657-663.
76 Kitao Y, Matsuyama T, Takano K, et al. Does ORP150/HSP12A protect dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity? Antioxid Redox Signal. 2007, [Epub ahead of print].
77 Kitao Y, Imai Y, Ozawa K, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet. 2007, 16(1):50-60.
78 Kobayashi T, Ohta Y. Enforced expression of oxygen-regulated protein, ORP150, induces vacuolar degeneration in mouse myocardium. Transgenic Res. 2003, 12(1):13-22.
79 Ikeda J, Kaneda S, Kuwabara K, et al. Cloning and expression of cDNA encoding the human 150kDa oxygen-regulated protein, ORP150. Biochem Biophys Res Commnu. 1997, 230(1):94-99.
80 Vasiliou V, Pappa A, Peterson DR. Role of aldehyde dehydrogenases in endogenous and xenobiotic metablism. Chem Biol Interact. 2000, 129(1-2):1-19.
81 Marchitti SA, Orlicky DJ, Vasiliou V. Expression and initial characterization of human ALDH3B1. Biochem Biophys Res Commnu. 2007, 356(3):792-798.
82 Galter D, Buervenich S, Carmine S, et al. ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia. Neurobiol Dis. 2003, 14(3):637-647.
83 Leiphon LJ, Picklo MJ Sr. Inhibition of aldehyde detoxification in CNS mitochondria by fungicides. Neurotoxicology. 2007, 28(1):143-149.
84 Florang VR, Rees JN, Brogden NK, et al. Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal. Neurotoxicology. 2007, 28(1):76-82.
85 Jeng JJ, Weiner H. Purification and characterization of catalytically active precursor of rat liver mitochondrial aldehyde dedydrogenases expressed in Escherichia coli. Arch Biochem Biophys. 1991, 289(1):214-222.
86 Siever DA, Erickson HP. Extracellular annexin II. Int J Biochem Cell Biol. 1997, 29(11):1219-1223.
87 黄昀, 傅松滨. Annexin II 的遗传学研究. 国外医学遗传学分册. 2004, 27(6):330-333.
88 Goulet F, Moore KG, Sartorelli AC. Glycosylation of annexin I and annexin II. Biochem Biophys Res Commun. 1992, 188(2):554-558.
1. 张德刚 , 赵瑛 . 氧化应激与糖尿病神经病变 . 医学综述 . 2006, 12(6):990-993.
2. 池 泉 , 黄 开 勋 . 蛋 白 质 酪 氨 酸 硝 化 的 研 究 . 化 学 进 展 . 2006. 18(7/8):1019-1025.
3. Gorg B, Ovartskhava N, Voss P, et al. Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration. FEBS Lett. 2007, 581(1):84-90
4. Ghezzi P, Bonetto V. Redox proteomics: identification of oxidatively modified proteins. Proteomics. 2003, 3(7):1145-1153.
5. 瞿 苏 , 王 友 群 . 泛 素 非 经 典 通 路 的 研 究 . 医 学 综 述 . 2006, 12(17):1039-1041.
6. McNaught KS, Olanow CW. Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson′s disease. Ann Neurol. 2003, 53(Suppl 3):73-86.
7. Souza JM, Choi I, Chen Q, et al. Proteolytic degradation of tyrosine nitrated proteins. Arch Biochem Biophys. 2000, 380(2):360-366.
8. Buchczyk DP, Grune T, Sies H, et al. Modifications of glyceraldehyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by 20S proteasome. Biol Chem. 2003, 384(2):237-241.
9. Hyun DH, Lee M, Halliwell B, et al. Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J Neurochem. 2003, 86(2):363-373.
10. Hyun DH, Gray DA, Halliwell B, et al. Interference with ubiquitination causes oxidative damage and increased protein nitration: implications for neurodegenerative diseases. J Neurochem. 2004, 90(2):422-430.
11. Bar-Shai M, Reznick AZ. Peroxynitrite induces an alternative NF-kappaB activation pathway in L8 rat myoblasts. Antioxid Redox Signal. 2006, 8(3-4):639-652.
12. Bar-Shai M, Reznick AZ. Reactive nitrogen species induce nuclear factor-kappaB-mediated protein degradation in skeletal muscle cells. Free Radic Biol Med. 2006, 40(12):2112-2125.
13. Sarchielli P, Galli F, Floridi A, et al. Relevance of protein nitration in brain injury: a key pathophysiological mechanism in neurodegenerative, autoimmune, or inflammatory CNS diseases and stroke. Amino Acids. 2003, 25(3-4):427-436.
14. Good PF, Hsu A, Werner P, et al. Protein nitration in Parkinson's disease. J Neuropathol Exp Neurol. 1998, 57(4):338-342.
15. Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinophy lesions. Science. 2001, 291(5504):595-597.
16. Aoyama K, Matsubara K, Fujikawa Y, et al. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol. 2000, 47(4):524-527.
17. Gatto EM, Riobo NA, Carreras MC, et al. Overexpression of neuronal nitric oxide synthase in Parkinson’s disease. Nitric Oxide. 2000, 4(5):534-9.
18. Przedborski S, Jackson-Lewis V. Mechanisms of MPTP toxicity. Mov Disord. 1998, 13(Suppl 1):35-38.
19. Riobo NA, Schopfer FJ, Boveris AD, et al. The reaction of nitric oxide with 6-hydroxydopamine: implications for Parkinson’s disease. Free Radic Biol Med. 2002, 32(2):115-121.
20. Shavali S, Combs CK, Ebadi M. Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronalcells in co-culture: relevance to Parkinson's disease. Neurochem Res. 2006, 31(1):85-94.
21. Trostchanskv A, Rubbo H. Lipid nitration and formation of lipid-protein adducts: biological insights. Amino Acids. 2006, [Epub ahead of print].
22. Bharath S, Andersen JK. Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line results in limited tyrosine nitration of mitochondrial complex I subunits: implications for Parkinson's disease. Antioxid Redox Signal. 2005, 7(7-8):900-910.
23. Lee SJ, Kim DC, Choi BH, et al. Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J Biol Chem. 2006, 281(4):2215-2224.
24. Park TH, Kim DH, Kim CH, et al. Peroxynitrite scavenging mode of alaternin isolated from Cassia tora. J Pharm Pharmacol. 2004 , 56(10):1315-1321.
25. Selley ML. Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res. 2005, 1037(1-2):1-6.
26. Ebadi M, Brown-Borg H, El Refaey H, et al. Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson disease. Brain Res Mol Brain Res. 2005, 134(1):67-75.
27. 韩威, 张颖, 杜丹华等. alpha-synuclein 在帕金森病发病机制中的作用. 上海医学. 2006, 29(7):501-504.
28. Takahashi T, Yamashita H, Nakamnura T, et al. Tyrosine 125 of alpha-synuclein plays a critical role for dimerization following nitrativestress. Brain Res. 2002, 938(1-2):73-80.
29. Yamin G, Uverskv VN, Fink AL. Nitration inhibits fibrillation of human alpha-synuclein in vitro by formation of soluble oligomers. FEBS Lett. 2003, 542(1-3):147-152.
30. Uverskv VN, Yamin G, Munishkina LA, et al. Effect of nitration on the structure and aggregation of alpha-synuclein. Brain Res Mol Brain Res. 2005, 134(1):84-102.
31. Hodara R, Norris EH, Giasson BI, et al. Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J Biol Chem. 2004, 279(46):47746-47753.
32. Mishizen-Eberz AJ, Norris EH, Giasson BI, et al. Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein. Biochemistry. 2005, 44(21):7818-7829.
1. Grunblatt E, Mandel S, Jacob-Hirsch J, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm. 2004, 111(12):1543-1573.
2. 杨策, 王正国, 朱佩芳. 蛋白质组中蛋白质磷酸化研究进展. 生理科学进展. 2004, 35(2):119-124.
3. 张丽君. 磷酸化蛋白质的检测技术进展. 国外医学临床生物化学与检验学分册. 2005, 26(5):290-292.
4. 刘亚伟, 戴兵, 梅长林. 质谱技术分析磷酸化蛋白的研究进展. 医学分子生物学杂志. 2006, 3(1):73-76.
5. Jullien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998, 61:1-23.
6. Forno LS, Sternberger LA, Sternberger NH, et al. Reaction of Lewy bodies with antibodies to phosphorylated and non-phosphorylated neurofilaments. Neurosci Lett. 1986, 64(3):253-258.
7. Hill WD, Lee VM, Hurtig HI, et al. Epitopes located in spatially separate domains of each neurofilament subunit are present in Parkinson’s disease Lewy bodies. J Comp Neurol. 1991, 309(1):150-160.
8. Gai WP, Vickers JC, Blumbergs PC, et al. Loss of non-phosphorylated neurofilament immunoreactivity with preservation of tyrosine hydroxylase in surviving substantia nigra neurons in Parkinson’s disease. J NeurolNeurosurg Psychiatry. 1994, 57(9):1039-1046.
9. Brion JP, Couck AM. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Am J Pathol. 1995, 147(5):1465-1476.
10. Iwatsubo T, Nakano I, Fukunaga K, et al. Ca2+/calmodulin-dependent protein kinase II immunoreactivity in Lewy bodies. Acta Neuropathol (Berl). 1991, 82(3):159-163.
11. Nagatsu T. Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Essays Biochem. 1995, 30:15-35.
12. Perez RG, Waymire JC, Lin E, et al. A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci. 2002, 22(8):3090-3099.
13. Chuenkova MV, Pereiraperrin M. Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi parasite-derived neurotrophic factor. Brain Res. 2006, 1099(1):167-175.
14. Okochi M, Walter J, Koyama A, et al. Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem. 2000, 275(1):390-397.
15. Kim EJ, Sung JY, Lee HJ, et al. Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion formation. J Biol Chem. 2006,
281(44):33250-33257.
16. Neumann M, Kahle PJ, Giasson BI, et al. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest. 2002, 110(10):1429-1439.
17. Yamada M, Iwatsubo T, Mizuno Y, et al. Overexpression of alpha-synucleinin rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. J Neurochem. 2004, 91(2):451-461.
18. Saito Y, Kawashima A, Ruberu NN, et al. Accumulation of phosphorylated alpha-synuclein in aging human brain. J Neuropathol Exp Neurol. 2003, 62(6):644-654.
19. Arawaka S, Wada M, Goto S, et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. J Neurosci. 2006, 26(36):9227-9238.
20. Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005, 8(5):657-663.
21. Saha AR, Hill J, Utton MA, et al. Parkinson's disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci. 2004, 117(7):1017-1024.
22. Lee G, Tanaka M, Park K, et al. Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1 interaction and inclusion body formation. J Biol Chem. 2004, 279(8):6834-6839.
23. Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
24. Frasier M, Walzer M, McCarthy L, et al. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol. 2005,192(2):274-287.
25. Kwok JB, Hallupp M, Loy CT, et al. GSK3B polymorphisms alter transcription and splicing in Parkinson's disease. Ann Neurol. 2005, 58(6);819-820.
26. Kozikowski AP, Gaisina IN, Petukhov PA, et al. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease. ChemMedChem. 2006, 1(2):256-266.
27. Nishino N, Kitamura N, Hashimoto T, et al. Transmembrane signaling systems in the brain of patients with Parkinson’s disease. Rev Neurosci. 1993, 4(2):213-222.
28. Cash R, Raisman R, Ploska A, et al. Dopamine D-1 receptor and cyclic AMP-dependent phosphorylation in Parkinson’s disease. J Neurochem. 1987, 49(4):1075-1083.
29. Oh JD, Vaughan CL, Chase TN. Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits. Brain Res. 1999, 821(2):433-442.
30. Dunah AW, Wang Y, Yasuda RP, et al. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson's disease. Mol Pharmacol. 2000, 57(2):342-352.
31. Chase TN, Oh JD. Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Ann Neurol. 2000, 47(4 Suppl 1):S122-129.
32. Dunah AW, Sirianni AC, Fienberg AA, et al. Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requiresFyn protein tyrosine kinase but not DARPP-32. Mol Pharmacol. 2004, 65(1):121-129.
33. Ba M, Kong M, Yang H, et al. Changes in subcellular distribution and phosphorylation of GluR1 in lesioned striatum of 6-hydroxydopamine-lesioned and l-dopa-treated rats. Neurochem Res. 2006, 31(11): 1337-1347.
34. Daily D, Barzilai A, Offen D, et al. The involvement of p53 in dopamine-induced apoptosis of cerebellar granule neurons and leukemic cells overexpressing p53. Cell Mol Neurobiol. 1999, 19(2):261-276.
35. Lee SJ, Kim DC, Choi BH, et al. Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J Biol Chem. 2006, 281(4):2215-2224.
36. Ryu EJ, Harding HP, Angelastro JM, et al. Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's disease. J Neurosci. 2002, 22(24):10690-10698.
37. Chen G, Bower KA, Ma C, et al. Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death. FASEB J. 2004, 18(10):1162-1164.
38. Avraham E, Szargel R, Eyal A, et al. Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation. J Biol Chem. 2005, 280(52):42877-42886.
39. Chalovich EM, Zhu JH, Caltagarone J, et al. Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J Biol Chem. 2006, 281(26):17870-17881.
40. West AB, Moore DJ, Biskup S, et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005, 102(46):16842-16847.
41. Gloeckner CJ, Kinkl N, Schumacher A, et al. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Gent. 2006, 15(2):223-232.
42. Sim CH, Lio DS, Mok SS, et al. C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum Mol Genet. 2006, 15(21):3251-3262.
43. Panet H, Barzilai A, Daily D, et al. Activation of nuclear transcription fator kappa B (NF-kappaB) is essential for dopamine-induced apoptosis in PC12 cells. J Neurochem. 2001, 77(2):391-398.
44. Wilms H, Rosenstiel P, Sievers J, et al. Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J. 2003, 17(3):500-502.
45. Noda K, Kitami T, Gai WP, et al. Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease. Biochem Biophys Res Commun. 2005, 331(1):309-317.
46. Kulich SM, Chu CT. Sustained extracellular signal-regulated kinase activation by 6-hydroxydopamine: implications for Parkinson's disease. J Neurochem. 2001, 77(4):1058-1066.
47. Gomez-Santos C, Ferrer I, Reiriz J et al. MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastomaSH-SY5Y cells. Brain Res. 2002, 935(1-2):32-39.
48. Lipman T, Tabakman R, Lazarovici P. Neuroprotective effects of the stable nitroxide compound Tempol on 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in the Nerve Growth Factor-differentiated model of pheochromocytoma PC12 cells. Eur J Pharmacol. 2006, 549(1-3):50-57.
49. Niso-Santano M, Moran JM, Garcia-Rubio L, et al. Low concentrations of paraquat induces early activation of extracellular signal-regulated kinase 1/2, protein kinase B, and c-Jun N-terminal kinase 1/2 pathways: role of c-Jun N-terminal kinase in paraquat-induced cell death. Toxicol Sci. 2006, 92(2):507-515.
50. Choi HJ, Lee SY, Cho Y, et al. JNK activation by tetrahydrobiopterin: implication for Parkinson's disease. J Neurosci Res. 2004, 75(5):715-721.
51. Silva RM, Kuan CY, Rakic P, et al. Mixed lineage kinase-c-Jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease. Mov Disord. 2005, 20(6):653-664.
1. 朱立平 . 蛋白质糖基化与 B 细胞免疫 . 上海免疫学杂志 . 2001, 21(4):193-194.
2. 周吉军, 吴玉章. 蛋白糖基化与细胞毒性 T 淋巴细胞应答. 第三军医大学学报. 2000, 22(10):997-1003.
3. 章晓联. 蛋白糖基化与免疫. 中国免疫学杂志. 2004, 20(4):290-293.
4. 蒯学章, 张令强, 贺福初. O-GlcNAc 修饰研究进展. 军事医学科学院院刊. 2006, 30(1):68-72.
5. Parodi AJ. Role of N-oligosaccharide endoplasmic reticulum processing reactions in glycoprotein folding and degradation. Biochem J. 2000, 348 (1):1-13.
6. Frenkel Z, Gregory W, Kornfeld S et al. Endoplasmic reticulum-associated degradation of mammalian glycoproteins involves sugar chain trimming to Man6-5GlcNAc2. J Biol Chem. 2003, 278(36):34119-34124.
7. Mancini R, Fagioli C, Fra AM et al. Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events. FASEBJ. 2000, 14(5):769-778.
8. Yoshida Y, Chiba T, Tokunaga F. E3 ubiquitin ligase that recognizes sugarchains. Nature. 2002, 418(6896):438-442.
9. Karaivanova VK, Spiro RG. Effect of proteasome inhibitors on the release into the cytosol of free polymannose oligosaccharides from glycoproteins. Glycobiology. 2000, 10(7):727-735.
10. Suzuki T. A simple, sensitive in vitro assay for cytoplasmic deglycosylation by peptide: N-glycanase. Methods. 2005, 35(4):360-365.
11. Katiyar S, Li G, Lennarz WJ. A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2004, 101(38):13774-13779.
12. Sumegi M, Hunyadi-Gulyas E, Medzihradszky KF, et al. 26S proteasome subunits are O-linked N-acetylglucosamine-modified in Drosophila melanogaster. Biochem Biophys Res Commun. 2003, 312(4):1284-1289.
13. Zachara NE, Hart GW. O-GlcNAc modification: a nutritional sensor that modulates proteasome function. Trends Cell Biol. 2004, 14(5):218-221.
14. Jorgensen JP, Lauridsen AM, Kristensen P, et al. Adrm1, a putative cell adhesion regulating protein, is a novel proteasome-associated factor. J Mol Biol. 2006, 360(5):1043-1052.
15. Guinez C, Lemoine J, Michalski JC, et al. 70-kDa-heat shock protein presents an adjustable lectinic activity towards O-linked N-acetylglucosamine. Biochem Biophys Res Commun. 2004, 319(1):21-26.
16. Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
17. Shimura H, Schlossmacher MG, Hattori N, et al. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001, 293(5528):263-269.
18. Goldknopf IL, Sheta EA, Bryson J, et al. Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem Biophys Res Commun. 2006, 342(4):1034-1039.
19. Kim YS, Lee SJ. Novel covalent modifications of alpha-synuclein during the recovery from proteasomal dysfunction. Biochem Biophys Res Commun. 2006, 346(4):1312-1319.
2 Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science. 2000, 290(5493): 985-989.
3 Przedborski S, Chen Q, Vila M, et al. Oxidative post-translational modifications of a-synuclein in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J Neurochem. 2001, 76(2): 637-640.
4 Aoyama K, Matsubara K, Fujikawa Y, et al. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol. 2000, 47(4):524-527.
5 Gatto EM, Riobo NA, Carreras MC, et al. Overexpression of neuronal nitric oxide synthase in Parkinson’s disease. Nitric oxide. 2000, 4(5):534-539.
6 Castegna A, Thongboonkerd V, Klein JB, et al. Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem. 2003, 85(6):1394-1401.
7 Maruyama Y, Teraoka H, Iwata H, et al. Inhibitory effects of endogenous dopaminergic neurotoxin, norsalsolinol on dopamine secretion in PC12 rat pheochromocytoma cells. Neurochem Int. 2001, 38(7):567-572.
8 Wang JJ, Zhang T, Niu DB, et al. Doxycycline-regulated co-expression ofGDNF and TH in PC12 cells. Neurosci Lett. 2006, 401(1-2):142-145.
9 Wei Q, Yeung M, Jurma OP, et al. Genetic elevation of monoamine oxidase levels in dopaminergic PC12 cells results in increased free radical damage and sensitivity to MPTP. J Neurosci Res. 1996, 46(6):666-673.
10 Jha N, Kumar MJ, Boonplueang R, et al. Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin protein degradation pathway: relevance for Parkinson’s disease? J Neurochem. 2002, 80(4):555-561.
11 McNaught KS, Olanow CW, Halliwell B, et al. Failure of the ubiquitin-proteasome system in Parkinson’s disease. Nat Rev Neurosci. 2001, 2(8):589-594.
12 Rideout HJ, Larsen KE, Sulzer D, et al. Proteasomal inhibition leads to formation of ubiquitin / α-synuclein - immunoreactive inclusions in PC12 cells. J Neurochem. 2001, 78(4):899-908.
13 McNaught KS, Perl DP Brownell AL, et al. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson’s disease. Ann Neurol. 2004, 56(1):149-162.
14 Ross CA, Pickart CM. The ubiquitin-proteasome pathway in Parkinson’s disease and other neurodegenerative diseases. Trends Cell Biol. 2004, 14(12):703-711.
15 McNaught KS, Jackson T, JnoBaptiste R, et al. Proteasome dysfunction in sporadic Parkinson’s disease. Neurology. 2006, 66(10 Suppl 4):S37-S49.
16 Macario AJ, Grippo TM, de Macario EC. Genetic disorders involving molecular-chaperone genes: a perspective. Genet Med. 2005, 7(1):3-12.
17 张磊, 陈秋惠, 常明等. 蛋白质组学技术对 PC12 细胞热休克蛋白的鉴定.中国老年学杂志. 2006, 26(10):1400-1401.
18 Roobol A, Sahyoun ZP, Carden MJ. Selected subunits of the cytosolic chaperonin associate with microtubules assembled in vitro. J Biol Chem. 1999, 274(4):2408-2415.
19 Yokata S, Yanagi H, Yura T, et al. Cytosilic chaperonin-containing t-complex polypeptide 1 changes the content of a particular subunit species concomitant with substrate binding and folding activities during the cell cycle. Eur J Biochem. 2001, 268(17):4664-4673.
20 Shirvan A, Ziv I, Barzilai A, et al. Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons. J Neural Transm Suppl. 1997, 50:67-78.
21 Horiguchi R, Dohra H, Tokumoto T. Comparative proteome analysis of changes in the 26S proteasome during oocyte maturation in goldfish. Proteomics. 2006, 6(14):4195-4202.
22 Demand J, Lüders J, H?hfeld J. The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperon cofactors. Mol Cell Biol. 1998, 18(4):2023-2028.
23 张磊, 许忠, 常明等. 蛋白质组学技术鉴定的 PC12 细胞细胞骨架蛋白. 脑与神经疾病杂志. 2006, 14(3):190-192.
24 Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
25 Frasier M, Walzer M, McCarthy L, et al. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol. 2005,192(2):274-287.
26 Zastrow MS, Vlcek S, Wilson KL. Proteins that bind A-type lamins: integrating isolated clues. J Cell Sci. 2004, 117(7):979-987.
27 宁钧宇, 由江峰, 裴斐等. G3BP 单克隆抗体制备及 G3BP 在肿瘤组织中表达的检测. 2005, 34(4):215-219.
28 Grunblatt E, Mandel S, Jacob-Hirsch J, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm. 2004, 111(12):1543-1573.
29 Jullien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998, 61:1-23.
30 Brion JP, Couck AM. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Am J Pathol. 1995, 147(5):1465-1476.
31 Iwatsubo T, Nakano I, Fukunaga K, et al. Ca2+/calmodulin-dependent protein kinase II immunoreactivity in Lewy bodies. Acta Neuropathol (Berl). 1991, 82(3):159-163.
32 Okochi M, Walter J, Koyama A, et al. Constitutive phosphorylation of the Parkinson’s disease Associated α-synuclein. J Biol Chem. 2000, 275(1):390-397.
33 Iwatsubo T. Aggregation of α-synuclein in the pathogenesis of Parkinson’s disease. J Neurol. 2003, 250(Suppl 3): III/11-III/14.
34 Lee G, Tanaka M, Park K, et al. Casein kinase II-mediated phosphorylation regulates α-synuclein / synphilin-1 interaction and inclusion body formation.J Biol Chem. 2004, 279(8):6834-6839.
35 Wu DC, Teismann P, Tieu K, et al. NADPH oxidase mediates oxidative stress in the 1-methyl-4- phenyl - 1,2,3,6 - tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci USA. 2003, 100(10):6145-6150.
36 Steinberg TH, Agnew BJ, Gee KR, et al. Global quantitative phosphoprotein analysis using multiplexed proteomics technology. Proteomics. 2003, 3(7):1128-1144.
37 Yuan X, Simpson P, McKeown C, et al. Structure, dynamics and interactions of p47, a major adaptor of the AAA ATPase, p97. EMBO J. 2004, 23(7):1463-1473.
38 Uchiyama K, Kondo H. p97/p47-mediated biogenesis of Golgi and ER. J Biochem (Tokyo). 2005, 137(2):115-119.
39 Kano F, Kondo H, Yamamoto A, et al. The maintenance of the endoplasmic reticulum network is regulated by p47, a cofactor of p97, through phosphorylation by cdc2 kinase. Genes Cells. 2005, 10(4):333-344.
40 Uchiyama K, Jokitalo E, Lindman M, et al. The localization and phosphorylation of p47 are important for Golgi disassembly-assembly during the cell cycle. J Cell Biol. 2003, 161(6):1067-1079.
41 Hirabayashi M, Inoue K, Tanaka K, et al. VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration. Cell Death Differ. 2001, 8(10):977-984.
42 Wójcik C, Yano M, DeMartino GN. RNA interference of valosin-containing protein(VCP/p97) reveals multiple cellular roles linked to ubiquitin/proteasome-dependent proteolysis. J Cell Sci. 2004, 117 (2):281-292.
43 Nagahama M, Suzuki M, Hamada Y, et al. SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation. Mol Biol Cell. 2003, 14(1): 262-273.
44 Hartmann-Petersen R, Wallace M, Hofmann K, et al. The Ubx2 and Ubx3 cofactors direct Cdc48 activity to proteolytic and nonproteolytic ubiquitin-dependent processes. Curr Biol. 2004, 14(9):824-828.
45 Parcellier A, Schmitt E, Brunet M, et al. Small heat shock proteins HSP27 and αB-Crystallin: cytoprotective and oncogenic functions. Antioxid Redox Signal. 2005, 7(3-4):404-413.
46 Gorman AM, Szegezdi E, Quigney DJ, et al. Hsp27 inhibits 6-hydroxydopamine-induced cytochrome c release and apoptosis in PC12 cells. Biochem Biophys Res Commnu. 2005, 327(3):801-810.
47 Ito H, Kamei K, Iwamoto I, et al. Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J Biochem. 2002, 131(4):593-603.
48 Fujisawa H, Okuno S. Regulatory mechanism of tyrosine hydroxylase activity. Biochem Biophys Res Commnu. 2005, 338(1):271-276.
49 Kaufman S. Tyrosine hydroxylase. Adv Enzymol Relat Areas Mol Biol. 1995,70:103-220.
50 Mori F, Nishie M, Kakita A, et al. Relationship among α-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. J Neuropathol Exp Neurol. 2006, 65(8):808-815.
51 Chuenkova MV, Pereiraperrin M. Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi parasite-derived neurotrophic factor. Brain Res. 2006, 1099(1):167-175.
52 张克忠, 王坚, 蒋雨平. Lactacystin 对酪氨酸羟化酶基因和蛋白表达的影响. 中国临床神经科学. 2005, 13(2):144-148.
53 Hyndman D, Bauman DR, Heredia VV. The aldo-keto reductase superfamily homepage. Chem Biol Interac. 2003, 143-144:621-631.
54 Allan D, Lohnes D. Cloning and developmental expression of mouse aldehyde reductase (AKR1A4). Mech Dev. 2000, 94(1-2):271-275.
55 Davydov VV, Dobaeva NM, Bozhkov AI. Possible role of alteration of aldehyde’s scavenger enzymes during aging. Exp Gerontol. 2004, 39(1):11-16.
56 周丹, 倪晓华. 核磷蛋白的生物学功能及其与肿瘤发生的关系. 生命的化学. 2006, 26(3):244-247.
57 Lim MJ, Wang XW. Nucleophosmin and human cancer. Cancer Detect Prev. 2006, 30(6):481-490.
58 Xiao S, McLean J, Robertson J. Neuronal intermediate filaments and ALS: a new look at an old question. Biochim Biophys Acta. 2006, 1762(11-12):1001-1012.
59 Petzold A. Neurofilament phosphoforms: surrogate markers for axonal injury, degeneration and loss. J Neurol Sci. 2005, 233(1-2):183-198.
60 Cairns NJ, Jaros E, Perry RH, et al. Temporal lobe pathology of human patients with neurofilament inclusion disease. Neurosci Lett. 2004, 354(3):245-247.
61 Kriz J, Beaulieu JM, Julien JP, et al. Up-regulation of peripherin is associated with alterations in synaptic plasticity in CA1 and CA3 regions of hippocampus. Neurobiol Dis. 2005, 18(2):409-420.
62 Huc C, Escurat M, Djabali K, et al. Phosphorylation of peripherin, anintermediate filament protein, in mouse neuroblastoma NIE 115 cell line and in sympathetic neurons. Biochem Biophys Res Commnu. 1989, 160(2):772-779.
63 Goldknopf IL, Sheta EA, Bryson J, et al. Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem Biophys Res Commun. 2006, 342(4):1034-1039.
64 Kim YS, Lee SJ. Novel covalent modifications of alpha-synuclein during the recovery from proteasomal dysfunction. Biochem Biophys Res Commun. 2006, 346(4):1312-1319.
65 Wu J, Lenchik NJ, Pabst MJ, et al. Functional characterization of two-dimensional gel-separated proteins using sequential staining. Electrophoresis. 2005, 26(1):225-237.
66 Yu LG, Andrews N, Weldon M, et al. An N-terminal truncated form of Orp150 is a cytoplasmic ligand for the anti-proliferative mushroom Agaricus bisporus lectin and is required for nuclear localization sequence-dependent nuclear protein import. J Biol Chem. 2002, 277(27):24538-24545.
67 Kuwabara K, Matsumoto M, Ikeda J, et al. Purification and characterization of a novel stress protein, the 150-kDa oxygen-regulated protein(ORP150), from cultured rat astrocytes and its expression in ischemic mouse brain. The Journal of Biological Chemistry. 1996, 271(9):5025-5032.
68 Tohyama M, Ogawa T. Stress response of cultured astrocytes to hypoxia/reoxygenation. Nippon Yakurigaku Zasshi. 1997, 109(3):145-151.
69 Bando Y, Ogawa S, Yamauchi A, et al. 150-kDa oxygen-regulated protein(ORP150) functions as a novel molecular chaperone in MDCK cells. Am J Physiol Cell Physiol. 2000, 278(6):1172-1182.
70 Tsukamoto Y, Kuwabara K, Hirota S, et al. 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein. J Clin Invest. 1996, 98(8):1930-1941.
71 Ozawa K, Tsukamoto Y, Hori O, et al. Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone. Cancer Res. 2001, 61(10): 4206-4213.
72 Miyazaki M, Ozawa K, Hori O, et al. Expression of 150-kd oxygen-regulated protein in the hippocampus suppresses delayed neuronal cell death. J Cereb Blood Flow Metab. 2002, 22(8):979-987.
73 Kitao Y, Ozawa K, Miyazaki M, et al. Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity. J Clin Invest. 2001, 108(10):1439-1450.
74 Kobayashi T, Ohta Y. 150-kD oxygen-regulated protein is an essential factor for insulin release. Pancreas. 2005, 30(4):299-306.
75 Ozawa K, Miyazaki M, Matsuhisa M, et al. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes. 2005, 54(3):657-663.
76 Kitao Y, Matsuyama T, Takano K, et al. Does ORP150/HSP12A protect dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity? Antioxid Redox Signal. 2007, [Epub ahead of print].
77 Kitao Y, Imai Y, Ozawa K, et al. Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. Hum Mol Genet. 2007, 16(1):50-60.
78 Kobayashi T, Ohta Y. Enforced expression of oxygen-regulated protein, ORP150, induces vacuolar degeneration in mouse myocardium. Transgenic Res. 2003, 12(1):13-22.
79 Ikeda J, Kaneda S, Kuwabara K, et al. Cloning and expression of cDNA encoding the human 150kDa oxygen-regulated protein, ORP150. Biochem Biophys Res Commnu. 1997, 230(1):94-99.
80 Vasiliou V, Pappa A, Peterson DR. Role of aldehyde dehydrogenases in endogenous and xenobiotic metablism. Chem Biol Interact. 2000, 129(1-2):1-19.
81 Marchitti SA, Orlicky DJ, Vasiliou V. Expression and initial characterization of human ALDH3B1. Biochem Biophys Res Commnu. 2007, 356(3):792-798.
82 Galter D, Buervenich S, Carmine S, et al. ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia. Neurobiol Dis. 2003, 14(3):637-647.
83 Leiphon LJ, Picklo MJ Sr. Inhibition of aldehyde detoxification in CNS mitochondria by fungicides. Neurotoxicology. 2007, 28(1):143-149.
84 Florang VR, Rees JN, Brogden NK, et al. Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal. Neurotoxicology. 2007, 28(1):76-82.
85 Jeng JJ, Weiner H. Purification and characterization of catalytically active precursor of rat liver mitochondrial aldehyde dedydrogenases expressed in Escherichia coli. Arch Biochem Biophys. 1991, 289(1):214-222.
86 Siever DA, Erickson HP. Extracellular annexin II. Int J Biochem Cell Biol. 1997, 29(11):1219-1223.
87 黄昀, 傅松滨. Annexin II 的遗传学研究. 国外医学遗传学分册. 2004, 27(6):330-333.
88 Goulet F, Moore KG, Sartorelli AC. Glycosylation of annexin I and annexin II. Biochem Biophys Res Commun. 1992, 188(2):554-558.
1. 张德刚 , 赵瑛 . 氧化应激与糖尿病神经病变 . 医学综述 . 2006, 12(6):990-993.
2. 池 泉 , 黄 开 勋 . 蛋 白 质 酪 氨 酸 硝 化 的 研 究 . 化 学 进 展 . 2006. 18(7/8):1019-1025.
3. Gorg B, Ovartskhava N, Voss P, et al. Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration. FEBS Lett. 2007, 581(1):84-90
4. Ghezzi P, Bonetto V. Redox proteomics: identification of oxidatively modified proteins. Proteomics. 2003, 3(7):1145-1153.
5. 瞿 苏 , 王 友 群 . 泛 素 非 经 典 通 路 的 研 究 . 医 学 综 述 . 2006, 12(17):1039-1041.
6. McNaught KS, Olanow CW. Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson′s disease. Ann Neurol. 2003, 53(Suppl 3):73-86.
7. Souza JM, Choi I, Chen Q, et al. Proteolytic degradation of tyrosine nitrated proteins. Arch Biochem Biophys. 2000, 380(2):360-366.
8. Buchczyk DP, Grune T, Sies H, et al. Modifications of glyceraldehyde-3-phosphate dehydrogenase induced by increasing concentrations of peroxynitrite: early recognition by 20S proteasome. Biol Chem. 2003, 384(2):237-241.
9. Hyun DH, Lee M, Halliwell B, et al. Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J Neurochem. 2003, 86(2):363-373.
10. Hyun DH, Gray DA, Halliwell B, et al. Interference with ubiquitination causes oxidative damage and increased protein nitration: implications for neurodegenerative diseases. J Neurochem. 2004, 90(2):422-430.
11. Bar-Shai M, Reznick AZ. Peroxynitrite induces an alternative NF-kappaB activation pathway in L8 rat myoblasts. Antioxid Redox Signal. 2006, 8(3-4):639-652.
12. Bar-Shai M, Reznick AZ. Reactive nitrogen species induce nuclear factor-kappaB-mediated protein degradation in skeletal muscle cells. Free Radic Biol Med. 2006, 40(12):2112-2125.
13. Sarchielli P, Galli F, Floridi A, et al. Relevance of protein nitration in brain injury: a key pathophysiological mechanism in neurodegenerative, autoimmune, or inflammatory CNS diseases and stroke. Amino Acids. 2003, 25(3-4):427-436.
14. Good PF, Hsu A, Werner P, et al. Protein nitration in Parkinson's disease. J Neuropathol Exp Neurol. 1998, 57(4):338-342.
15. Giasson BI, Duda JE, Murray IV, et al. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinophy lesions. Science. 2001, 291(5504):595-597.
16. Aoyama K, Matsubara K, Fujikawa Y, et al. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann Neurol. 2000, 47(4):524-527.
17. Gatto EM, Riobo NA, Carreras MC, et al. Overexpression of neuronal nitric oxide synthase in Parkinson’s disease. Nitric Oxide. 2000, 4(5):534-9.
18. Przedborski S, Jackson-Lewis V. Mechanisms of MPTP toxicity. Mov Disord. 1998, 13(Suppl 1):35-38.
19. Riobo NA, Schopfer FJ, Boveris AD, et al. The reaction of nitric oxide with 6-hydroxydopamine: implications for Parkinson’s disease. Free Radic Biol Med. 2002, 32(2):115-121.
20. Shavali S, Combs CK, Ebadi M. Reactive macrophages increase oxidative stress and alpha-synuclein nitration during death of dopaminergic neuronalcells in co-culture: relevance to Parkinson's disease. Neurochem Res. 2006, 31(1):85-94.
21. Trostchanskv A, Rubbo H. Lipid nitration and formation of lipid-protein adducts: biological insights. Amino Acids. 2006, [Epub ahead of print].
22. Bharath S, Andersen JK. Glutathione depletion in a midbrain-derived immortalized dopaminergic cell line results in limited tyrosine nitration of mitochondrial complex I subunits: implications for Parkinson's disease. Antioxid Redox Signal. 2005, 7(7-8):900-910.
23. Lee SJ, Kim DC, Choi BH, et al. Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J Biol Chem. 2006, 281(4):2215-2224.
24. Park TH, Kim DH, Kim CH, et al. Peroxynitrite scavenging mode of alaternin isolated from Cassia tora. J Pharm Pharmacol. 2004 , 56(10):1315-1321.
25. Selley ML. Simvastatin prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced striatal dopamine depletion and protein tyrosine nitration in mice. Brain Res. 2005, 1037(1-2):1-6.
26. Ebadi M, Brown-Borg H, El Refaey H, et al. Metallothionein-mediated neuroprotection in genetically engineered mouse models of Parkinson disease. Brain Res Mol Brain Res. 2005, 134(1):67-75.
27. 韩威, 张颖, 杜丹华等. alpha-synuclein 在帕金森病发病机制中的作用. 上海医学. 2006, 29(7):501-504.
28. Takahashi T, Yamashita H, Nakamnura T, et al. Tyrosine 125 of alpha-synuclein plays a critical role for dimerization following nitrativestress. Brain Res. 2002, 938(1-2):73-80.
29. Yamin G, Uverskv VN, Fink AL. Nitration inhibits fibrillation of human alpha-synuclein in vitro by formation of soluble oligomers. FEBS Lett. 2003, 542(1-3):147-152.
30. Uverskv VN, Yamin G, Munishkina LA, et al. Effect of nitration on the structure and aggregation of alpha-synuclein. Brain Res Mol Brain Res. 2005, 134(1):84-102.
31. Hodara R, Norris EH, Giasson BI, et al. Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation. J Biol Chem. 2004, 279(46):47746-47753.
32. Mishizen-Eberz AJ, Norris EH, Giasson BI, et al. Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein. Biochemistry. 2005, 44(21):7818-7829.
1. Grunblatt E, Mandel S, Jacob-Hirsch J, et al. Gene expression profiling of parkinsonian substantia nigra pars compacta; alterations in ubiquitin-proteasome, heat shock protein, iron and oxidative stress regulated proteins, cell adhesion/cellular matrix and vesicle trafficking genes. J Neural Transm. 2004, 111(12):1543-1573.
2. 杨策, 王正国, 朱佩芳. 蛋白质组中蛋白质磷酸化研究进展. 生理科学进展. 2004, 35(2):119-124.
3. 张丽君. 磷酸化蛋白质的检测技术进展. 国外医学临床生物化学与检验学分册. 2005, 26(5):290-292.
4. 刘亚伟, 戴兵, 梅长林. 质谱技术分析磷酸化蛋白的研究进展. 医学分子生物学杂志. 2006, 3(1):73-76.
5. Jullien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol. 1998, 61:1-23.
6. Forno LS, Sternberger LA, Sternberger NH, et al. Reaction of Lewy bodies with antibodies to phosphorylated and non-phosphorylated neurofilaments. Neurosci Lett. 1986, 64(3):253-258.
7. Hill WD, Lee VM, Hurtig HI, et al. Epitopes located in spatially separate domains of each neurofilament subunit are present in Parkinson’s disease Lewy bodies. J Comp Neurol. 1991, 309(1):150-160.
8. Gai WP, Vickers JC, Blumbergs PC, et al. Loss of non-phosphorylated neurofilament immunoreactivity with preservation of tyrosine hydroxylase in surviving substantia nigra neurons in Parkinson’s disease. J NeurolNeurosurg Psychiatry. 1994, 57(9):1039-1046.
9. Brion JP, Couck AM. Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclin-dependent kinase 5. Am J Pathol. 1995, 147(5):1465-1476.
10. Iwatsubo T, Nakano I, Fukunaga K, et al. Ca2+/calmodulin-dependent protein kinase II immunoreactivity in Lewy bodies. Acta Neuropathol (Berl). 1991, 82(3):159-163.
11. Nagatsu T. Tyrosine hydroxylase: human isoforms, structure and regulation in physiology and pathology. Essays Biochem. 1995, 30:15-35.
12. Perez RG, Waymire JC, Lin E, et al. A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci. 2002, 22(8):3090-3099.
13. Chuenkova MV, Pereiraperrin M. Enhancement of tyrosine hydroxylase expression and activity by Trypanosoma cruzi parasite-derived neurotrophic factor. Brain Res. 2006, 1099(1):167-175.
14. Okochi M, Walter J, Koyama A, et al. Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem. 2000, 275(1):390-397.
15. Kim EJ, Sung JY, Lee HJ, et al. Dyrk1A phosphorylates alpha-synuclein and enhances intracellular inclusion formation. J Biol Chem. 2006,
281(44):33250-33257.
16. Neumann M, Kahle PJ, Giasson BI, et al. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies. J Clin Invest. 2002, 110(10):1429-1439.
17. Yamada M, Iwatsubo T, Mizuno Y, et al. Overexpression of alpha-synucleinin rat substantia nigra results in loss of dopaminergic neurons, phosphorylation of alpha-synuclein and activation of caspase-9: resemblance to pathogenetic changes in Parkinson's disease. J Neurochem. 2004, 91(2):451-461.
18. Saito Y, Kawashima A, Ruberu NN, et al. Accumulation of phosphorylated alpha-synuclein in aging human brain. J Neuropathol Exp Neurol. 2003, 62(6):644-654.
19. Arawaka S, Wada M, Goto S, et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. J Neurosci. 2006, 26(36):9227-9238.
20. Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005, 8(5):657-663.
21. Saha AR, Hill J, Utton MA, et al. Parkinson's disease alpha-synuclein mutations exhibit defective axonal transport in cultured neurons. J Cell Sci. 2004, 117(7):1017-1024.
22. Lee G, Tanaka M, Park K, et al. Casein kinase II-mediated phosphorylation regulates alpha-synuclein/synphilin-1 interaction and inclusion body formation. J Biol Chem. 2004, 279(8):6834-6839.
23. Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
24. Frasier M, Walzer M, McCarthy L, et al. Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein. Exp Neurol. 2005,192(2):274-287.
25. Kwok JB, Hallupp M, Loy CT, et al. GSK3B polymorphisms alter transcription and splicing in Parkinson's disease. Ann Neurol. 2005, 58(6);819-820.
26. Kozikowski AP, Gaisina IN, Petukhov PA, et al. Highly potent and specific GSK-3beta inhibitors that block tau phosphorylation and decrease alpha-synuclein protein expression in a cellular model of Parkinson's disease. ChemMedChem. 2006, 1(2):256-266.
27. Nishino N, Kitamura N, Hashimoto T, et al. Transmembrane signaling systems in the brain of patients with Parkinson’s disease. Rev Neurosci. 1993, 4(2):213-222.
28. Cash R, Raisman R, Ploska A, et al. Dopamine D-1 receptor and cyclic AMP-dependent phosphorylation in Parkinson’s disease. J Neurochem. 1987, 49(4):1075-1083.
29. Oh JD, Vaughan CL, Chase TN. Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal NMDA receptor subunits. Brain Res. 1999, 821(2):433-442.
30. Dunah AW, Wang Y, Yasuda RP, et al. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson's disease. Mol Pharmacol. 2000, 57(2):342-352.
31. Chase TN, Oh JD. Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications. Ann Neurol. 2000, 47(4 Suppl 1):S122-129.
32. Dunah AW, Sirianni AC, Fienberg AA, et al. Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requiresFyn protein tyrosine kinase but not DARPP-32. Mol Pharmacol. 2004, 65(1):121-129.
33. Ba M, Kong M, Yang H, et al. Changes in subcellular distribution and phosphorylation of GluR1 in lesioned striatum of 6-hydroxydopamine-lesioned and l-dopa-treated rats. Neurochem Res. 2006, 31(11): 1337-1347.
34. Daily D, Barzilai A, Offen D, et al. The involvement of p53 in dopamine-induced apoptosis of cerebellar granule neurons and leukemic cells overexpressing p53. Cell Mol Neurobiol. 1999, 19(2):261-276.
35. Lee SJ, Kim DC, Choi BH, et al. Regulation of p53 by activated protein kinase C-delta during nitric oxide-induced dopaminergic cell death. J Biol Chem. 2006, 281(4):2215-2224.
36. Ryu EJ, Harding HP, Angelastro JM, et al. Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's disease. J Neurosci. 2002, 22(24):10690-10698.
37. Chen G, Bower KA, Ma C, et al. Glycogen synthase kinase 3beta (GSK3beta) mediates 6-hydroxydopamine-induced neuronal death. FASEB J. 2004, 18(10):1162-1164.
38. Avraham E, Szargel R, Eyal A, et al. Glycogen synthase kinase 3beta modulates synphilin-1 ubiquitylation and cellular inclusion formation by SIAH: implications for proteasomal function and Lewy body formation. J Biol Chem. 2005, 280(52):42877-42886.
39. Chalovich EM, Zhu JH, Caltagarone J, et al. Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J Biol Chem. 2006, 281(26):17870-17881.
40. West AB, Moore DJ, Biskup S, et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005, 102(46):16842-16847.
41. Gloeckner CJ, Kinkl N, Schumacher A, et al. The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity. Hum Mol Gent. 2006, 15(2):223-232.
42. Sim CH, Lio DS, Mok SS, et al. C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1. Hum Mol Genet. 2006, 15(21):3251-3262.
43. Panet H, Barzilai A, Daily D, et al. Activation of nuclear transcription fator kappa B (NF-kappaB) is essential for dopamine-induced apoptosis in PC12 cells. J Neurochem. 2001, 77(2):391-398.
44. Wilms H, Rosenstiel P, Sievers J, et al. Activation of microglia by human neuromelanin is NF-kappaB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J. 2003, 17(3):500-502.
45. Noda K, Kitami T, Gai WP, et al. Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease. Biochem Biophys Res Commun. 2005, 331(1):309-317.
46. Kulich SM, Chu CT. Sustained extracellular signal-regulated kinase activation by 6-hydroxydopamine: implications for Parkinson's disease. J Neurochem. 2001, 77(4):1058-1066.
47. Gomez-Santos C, Ferrer I, Reiriz J et al. MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in human neuroblastomaSH-SY5Y cells. Brain Res. 2002, 935(1-2):32-39.
48. Lipman T, Tabakman R, Lazarovici P. Neuroprotective effects of the stable nitroxide compound Tempol on 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in the Nerve Growth Factor-differentiated model of pheochromocytoma PC12 cells. Eur J Pharmacol. 2006, 549(1-3):50-57.
49. Niso-Santano M, Moran JM, Garcia-Rubio L, et al. Low concentrations of paraquat induces early activation of extracellular signal-regulated kinase 1/2, protein kinase B, and c-Jun N-terminal kinase 1/2 pathways: role of c-Jun N-terminal kinase in paraquat-induced cell death. Toxicol Sci. 2006, 92(2):507-515.
50. Choi HJ, Lee SY, Cho Y, et al. JNK activation by tetrahydrobiopterin: implication for Parkinson's disease. J Neurosci Res. 2004, 75(5):715-721.
51. Silva RM, Kuan CY, Rakic P, et al. Mixed lineage kinase-c-Jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease. Mov Disord. 2005, 20(6):653-664.
1. 朱立平 . 蛋白质糖基化与 B 细胞免疫 . 上海免疫学杂志 . 2001, 21(4):193-194.
2. 周吉军, 吴玉章. 蛋白糖基化与细胞毒性 T 淋巴细胞应答. 第三军医大学学报. 2000, 22(10):997-1003.
3. 章晓联. 蛋白糖基化与免疫. 中国免疫学杂志. 2004, 20(4):290-293.
4. 蒯学章, 张令强, 贺福初. O-GlcNAc 修饰研究进展. 军事医学科学院院刊. 2006, 30(1):68-72.
5. Parodi AJ. Role of N-oligosaccharide endoplasmic reticulum processing reactions in glycoprotein folding and degradation. Biochem J. 2000, 348 (1):1-13.
6. Frenkel Z, Gregory W, Kornfeld S et al. Endoplasmic reticulum-associated degradation of mammalian glycoproteins involves sugar chain trimming to Man6-5GlcNAc2. J Biol Chem. 2003, 278(36):34119-34124.
7. Mancini R, Fagioli C, Fra AM et al. Degradation of unassembled soluble Ig subunits by cytosolic proteasomes: evidence that retrotranslocation and degradation are coupled events. FASEBJ. 2000, 14(5):769-778.
8. Yoshida Y, Chiba T, Tokunaga F. E3 ubiquitin ligase that recognizes sugarchains. Nature. 2002, 418(6896):438-442.
9. Karaivanova VK, Spiro RG. Effect of proteasome inhibitors on the release into the cytosol of free polymannose oligosaccharides from glycoproteins. Glycobiology. 2000, 10(7):727-735.
10. Suzuki T. A simple, sensitive in vitro assay for cytoplasmic deglycosylation by peptide: N-glycanase. Methods. 2005, 35(4):360-365.
11. Katiyar S, Li G, Lennarz WJ. A complex between peptide:N-glycanase and two proteasome-linked proteins suggests a mechanism for the degradation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2004, 101(38):13774-13779.
12. Sumegi M, Hunyadi-Gulyas E, Medzihradszky KF, et al. 26S proteasome subunits are O-linked N-acetylglucosamine-modified in Drosophila melanogaster. Biochem Biophys Res Commun. 2003, 312(4):1284-1289.
13. Zachara NE, Hart GW. O-GlcNAc modification: a nutritional sensor that modulates proteasome function. Trends Cell Biol. 2004, 14(5):218-221.
14. Jorgensen JP, Lauridsen AM, Kristensen P, et al. Adrm1, a putative cell adhesion regulating protein, is a novel proteasome-associated factor. J Mol Biol. 2006, 360(5):1043-1052.
15. Guinez C, Lemoine J, Michalski JC, et al. 70-kDa-heat shock protein presents an adjustable lectinic activity towards O-linked N-acetylglucosamine. Biochem Biophys Res Commun. 2004, 319(1):21-26.
16. Arima K, Hirai S, Sunohara N, et al. Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies. Brain Res. 1999, 843(1-2):53-61.
17. Shimura H, Schlossmacher MG, Hattori N, et al. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001, 293(5528):263-269.
18. Goldknopf IL, Sheta EA, Bryson J, et al. Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease. Biochem Biophys Res Commun. 2006, 342(4):1034-1039.
19. Kim YS, Lee SJ. Novel covalent modifications of alpha-synuclein during the recovery from proteasomal dysfunction. Biochem Biophys Res Commun. 2006, 346(4):1312-1319.