内质网应激与凋亡研究进展
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摘要
内质网是真核细胞中非常重要的一种细胞器,其在蛋白质的合成、折叠以及转运等过程中发挥重要作用,同时对细胞内环境和钙离子的变化非常敏感,可以调节细胞的应激水平和钙离子水平等。而一些病理因素如缺氧等都可能影响到内质网对于蛋白质前体的处理等过程从而诱发内质网应激反应(endoplas-mic reticulum stress response, ERS)和非折叠蛋白反应(unfolded protein reaction, UPR),甚至是造成细胞的凋亡。近年来,有研究证实一些人类疾病,如囊性纤维病、阿尔茨海默Aβ淀粉样斑等,都与内质网功能错乱有较大的关联,因此,了解内质网功能对人类疾病有较大意义,本综述主要对近年来关于内质网应激与凋亡方面的研究进行总结回顾。
Endoplasmic reticulum is an important organelle in eukaryotic cells, which plays an essential role in the process of protein synthesis, folding and transport. Meanwhile, it is sensitive to changes in the cellular environment and calcium ions, and can regulate cell stress and calcium levels. However, some pathological factors such as hypoxia might affect the endoplasmic reticulum process of protein precursors and other processes to induce endoplasmic reticulum stress response(ERS) and unfolded protein reaction(UPR), and even cause apoptosis. In recent years, some studies have confirmed that some human diseases, such as cystic fibrosis, Alzheimer's Aβamyloid plaques and so on, might have a greater association with dysfunction of the endoplasmic reticulum.Therefore, it might be significant to understand the function of the endoplasmic reticulum for human diseases. This review summarized recent studies on endoplasmic reticulum stress and apoptosis.
Endoplasmic reticulum is an important organelle in eukaryotic cells, which plays an essential role in the process of protein synthesis, folding and transport. Meanwhile, it is sensitive to changes in the cellular environment and calcium ions, and can regulate cell stress and calcium levels. However, some pathological factors such as hypoxia might affect the endoplasmic reticulum process of protein precursors and other processes to induce endoplasmic reticulum stress response(ERS) and unfolded protein reaction(UPR), and even cause apoptosis. In recent years, some studies have confirmed that some human diseases, such as cystic fibrosis, Alzheimer's Aβamyloid plaques and so on, might have a greater association with dysfunction of the endoplasmic reticulum.Therefore, it might be significant to understand the function of the endoplasmic reticulum for human diseases. This review summarized recent studies on endoplasmic reticulum stress and apoptosis.
引文
Acosta-A lvear D.,Zhou Y.,Blais A.,Tsikitis M.,Lents N.H.,Arias C.,Lennon C.J.,Kluger Y.,and Dynlacht B.D.,2007,XBP1 controls diverse cell type-and condition-specific transcriptional regulatory networks,Mol.Cell,27(1):53-66
Chen N.Z.,Jiang C.,and Li X.K.,2016,Role of endoplasmic reticulum stress in diseases,Zhongguo Shengwu Gongcheng Zazhi(China Biotechnology),36(1):76-85(陈娜子,姜潮,李校堃,2016,内质网应激与疾病,中国生物工程杂志,36(1):76-85)
Chen S.S.,He Z.Z.,Jiang S.X.,Xing J.J.,Lv X.Y.,and Lan H.Y.,2014,Cloning and expression analysis of calcium-dependent phosphokinase genes in Chenopodium album under stresses,Zhiwu Xuebao(Chinese Bulletin of Botany),49(2):139-149(陈莎莎,贺转转,姜生秀,邢佳佳,吕秀云,兰海燕,2014,藜钙依赖磷酸激酶基因CaCPK的克隆及胁迫表达,植物学报,49(2):139-149)
Fu Y.,Li Y.,Yang F.W.,and Lin S.D.,2013,The molecular mechanism and significance of autophagy induced by endoplasmic reticulum stress,Xiandai Shengwu Yixue Jinzhan(Progress in Modern Biomedicine),13(12):2393-2397(付裕,李滢,杨方万,林世德,2013,内质网应激诱导自噬的分子机制及意义,现代生物医学进展,13(12):2393-2397)
Han D.,Lerner A.G.,Walle L.V.,Upton J.P.,Xu W.,Hagen A.,Backes B.J.,Oakes S.A.,and Papa F.R.,2009,IRE1αkinase activation mod es contro l alternate endoribonuclease outputs to determine divergent cell fates,Cell,138(3):562-575
Hu N.B.,Sui Y.H.,He K.Q.,Wang M.M.,Zhang R.N.,Hu X.X.and Han X.T.,2016,Study of polysaccharides,organic acid amino acid and its compound on copigmentation of leaf pigment in purple pepper,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),36(3):715-720(胡能兵,隋益虎,何克勤,王蜜蜜,张若男,胡肖肖,韩小田2016,多糖、有机酸、氨基酸及其复配对紫色辣椒叶片色素辅色效果研究,基因组学与应用生物学,36(3):715-720)
Li X.C.,Fang L.,Li Z.J.,Devi P.N.,Chen F.,and Cai X.H.,2016Effect of endoplasmic reticulum stress in brain injury following chronic intermittent hypoxic in growing rats,Zhongguo Bingli Shengli Zazhi(Chinese Journal of Pathophysiology),32(8):1413-1418(李秀翠,方励,李志洁,POONITNeha Devi,陈帆,蔡晓红,2016,内质网应激在慢性间歇低氧幼鼠脑损害中的作用,中国病理生理杂志,32(8)1413-1418)
Lu S.J.,Yang Z.T.,Sun L.,Sun L.,Song Z.T.,and Liu J.X.2012,Conservation of IRE1 regulated bZIP74 m RNA unconventional splicing in rice(Oryza sativa L.)involved in ER stress responses,Mol.Plant,5(2):504-514
Ma T.,and Xue C.R.,2008,Endoplasmic reticulum stress and apoptosis,Yixue Zongshu(Medical Recapitulate),14(23):3565-3567(马涛,薛承锐,2008,内质网未折叠蛋白反应与凋亡信号机制研究进展,医学综述,14(23):3565-3567)
Mao T.,Yang L.,and Liu Y.,2011,Endoplasmic reticulum stress and metabolic dysfunction,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),33(7):727-737(毛婷,杨柳,刘勇,2011,细胞内质网应激与糖脂代谢紊乱的机制关联,中国细胞生物学学报,33(7):727-737)
Pan Y.J.,Wang Y.,Xu J.Q.,Wu J.F.,Yu S.Y.,Zeng G.F.,and Zhao G.J.,2016,Advance in the relationship between stero regulatory element-binding proteins and inflammation Shengwu Huaxue Yu Shengwu Wuli Jinzhan(Progress in Biochemistry and Biophysics),43(12):1146-1153(盘艳君王燕,徐健强,吴剑锋,喻思扬,曾高峰,赵国军,2016,固醇调节元件结合蛋白与炎症的关系研究进展,生物化学与生物物理进展,43(12):1146-1153)
Rui D.,Cui X.Z.,Ji W.Z.,Min J.J.,Ji Q.C.,and Ren J.L.,2014Expression and significance of unfolded protein response related factors(GRP78,ATF6 and XPB1)in human esophageal squamous cell carcinoma,Zhenduan Binglixue Zazhi(Chinese Journal of Diagnostic Pathology),21(5):293-296300(闰东,崔新征,吉文仲,闵建军,吉庆春,任景丽,2014未折叠蛋白反应相关因子GRP78、ATF6和XPB 1在人食管鳞状细胞癌中的表达及其意义,诊断病理学杂志,21(5):293-296,300)
Shaffer A.L.,Shapiro-Shelef M.,Iwakoshi N.N.,Lee A.H.,Qian S.B.,Zhao H.,Yu X.,Yang L.,Tan B.K.,Rosenwald A.,Hurt E.M.,Petroulakis E.,Sonenberg N.,Yewdell J.W.,Calame K.,Glimcher L.H.,and Staudt L.M.,2004,XBP1downstream of Blimp-1,expands the secretory apparatus and other organelles,and increases protein synthesis in plasma cell differentiation,Immunity,21(1):81-93
Song Y.,Yuan Y.Q.,and Yu J.,2013,Survery of study on endoplasmic reticulum stress perk apoptosis pathway,Zhonghua Zhongyiyao Xuekan(Chinese Archives of Traditional Chinese Medicine),31(5):1009-1011(宋洋,袁宜勤,郁洁,2013,内质网应激PERK凋亡通路研究进展,中华中医药学刊,31(5):1009-1011)
Su W.W.,Ding G.X.,Zhu C.H.,Yuan Y.G.,Zhang A.H.,and Huang S.M.,2011,Effect of knockdown of Sigma-1 receptor on endoplasmic reticulum stress and podocyte injury,Nanjin Yike Daxue Xuebao(Acta Universitatis Medicinalis Nanjing),31(5):667-672(苏维维,丁桂霞,朱春华,袁杨刚,张爱华,黄松明,2011,Sig-1R基因表达抑制对内质网应激和足细胞损伤的影响,南京医科大学学报,31(5):667-672)
Sun L.,Wang X.L.,Zhang Y.F.,Sun W.H.,Liu J.X.,and Song Z.T.,2018,The resistance analysis of Arabidopsis thaliana transcription factor NAC103 in the ER stress response,Fenzi Zhiwu Yuzhong(Molecular Plant Breedinge),16(5):1475-1481(孙玲,王晓蕾,张宇飞,孙卫红,刘建祥,宋泽婷,2018,拟南芥转录因子NAC103在内质网胁迫应答中的抗性分析,分子植物育种,16(5):1475-1481)
Wang H.,and Cai D.F.,2006,Ca2+and endoplasmic reticulum-induced apoptosis,Guoji Bingli Kexue Yu Linchuang Zazhi(International Journal of Pathology and Clinical Medicine),26(4):283-290(王虎,蔡定芳,2006,Ca2+与内质网途径的细胞凋亡,国际病理科学与临床杂志,26(4):283-290)
Wang W.D.,2017,Endoplasmic reticulum stress and kidney diseases,Zhongshan Daxue Xuebao(Journal of Sun Yat-sen University),38(2):196-203(王蔚东,2017,内质网应激与肾脏疾病,中山大学学报,38(2):196-203)
Wang Y.,Shen J.,Arenzana N.,Tirasophon W.,Kaufman R.J.,and Prywes R.,2000,Activation of ATF6 and an ATF6DNA binding site by the endoplasmic reticulum stress response,J.Biol.Chem.,275(35):27013-27020
Wei N.B.,Liu H.Y.,Wang H.F.,Ren D.X.,Liu J.X.,and Wang C.,2013,Research progress of mechanism of action of proteins in cholesterol metabolism of sterol regulatory element binding,Zhongguo Xumu Zazhi(Chinese Journal of Animal Science),49(5):80-84(魏宁波,刘红云,汪海峰,任大喜,刘建新,王翀,2013,固醇调控元件结合蛋白在胆固醇代谢中作用机制的研究进展,中国畜牧杂志,49(5):80-84)
Wu J.,and Zhang X.C.,2015,Research progress of UPR in hepatocellular carcinoma,Biaoji Mianyi Fenxi Yu Linchuang(Labeled Immunoassays and Clinical Medicine),22(3):233-236(吴健,张新晨,2015,未折叠蛋白反应在肝癌中的作用研究进展,标记免疫分析与临床,22(3):233-236)
Xia Y.N.,Li X.M.,Yuan N.N.,Zhang X.L.,and Tan Y.X.,2017Effect of hydrogen on endoplasmic reticulum stress and neural apoptosis in rats with cerebral ischemia-reperfusion injury,Chongqin Yiyuan(Chongqing Medicine),46(9):1159-1162,1167(夏裕宁,李雪梅,袁楠楠,张鑫磊,谭永星,2017氢气对大鼠局灶性脑缺血再灌注损伤内质网应激及神经细胞凋亡的影响,重庆医学,46(9):1159-1162,1167)
Xu M.,and Wang T.,2014,Endoplasmic reticulum stress and related molecular chaperones,Jiepou Xueke Jinzhan(Progress of Anatomical Sciences),20(4):381-384(徐盟,王涛,2014内质网应激反应与相关分子伴侣,解剖科学进展,20(4)381-384)
Xu T.,Shi N.,Wang L.,and Wang J.,2017,Changes of expressions of endoplasmic reticulum stress related molecules GRP78 and CHOP in neonatal mice with murine cytomegalovirus infection,Zhongguo Fuyou Baojian(Maternal and Child Health Care of China),32(1):152-156(许涛,师娜,王璐,王军,2017,内质网应激通路相关分子GRP78,CHOP在新生小鼠巨细胞病毒肝炎中的表达变化,中国妇幼保健,32(1):152-156)
Yang Z.T.,and Liu J.X.,2016,Endoplasmic reticulum stress response in plants,Shengwu Yishu Tongbao(Biotechnology Bulletin),32(10):84-96(杨正婷,刘建祥,2016,植物内质网胁迫应答研究进展,生物技术通报,32(10):84-96)
Yu R.J.,Zhang K.,Lv Z.M.,Liu Q.,and Hong Y.,2013,Effec of high fat diet and influence of melatonin on endoplasmic reticulum stress in mice epididymis,Zhongguo Zuzhi Huaxue Yu Xibao Huaxue Zazhi(Chinese Journal of Histochemistry and Cytochemistry),22(1):32-36(余荣娇,张凯,吕正梅,刘茜,洪燕,2013,高脂饮食对小鼠附睾内质网应激的影响及褪黑素的干预作用,中国组织化学与细胞化学杂志,22(1):32-36)
Zhang Y.,Meng F.Q.,Zhang Q.,and Bu H.,2016,changes of ATF6 expression in spinal cord of familial amyotrophic lateral sclerosis medol hSOD1G93Atransgenic mouse,Nao Yu Shenjing Jibing Zazhi(Journal of Brain and Nervous Diseases),24(3):160-165(张毓,孟凤琴,张蔷,卜晖,2016,内质网应激因子ATF6在hSOD1G93A转基因小鼠脊髓中的表达,脑与神经疾病杂志,24(3):160-165)
Zhao W.J.,Zhu H.F.,Zhou J.H.,Li X.Z.,Liu Y.N.,and Guo F.J.,2012,Impact of endoplasmic reticulum stress on regulation and control of XBP1 promoter transcription by ATF6,Ji efangjun Yixue Zazhi(Medical Journal of Chinese People's Liberation Army),37(4):317-321(赵文君,朱慧芳,周菁华,李祥柱,刘艳娜,郭风劲,2012,内质网应激对ATF6调控XBP1启动子转录的影响,解放军医学杂志,37(4):317-321)
Zhu J.,Piao R.L.,and Gao R.P.,2012,Toll-like receptor 4 signaling pathway and pancreatitis,Shijie Huaren Xiaohua Zazhi(World Chinese Journal of Digestology),20(4):271-275(朱杰,朴荣利,高润平,2012,TLR4信号传导通路与胰腺炎,世界华人消化杂志,20(4):271-275)
Zou Z.X.,and Li J.,2017,Endoplasmic reticulum stress and renal fibrosis,Hainan Yixue(Hainan Medical Journal),28(4):615-617(邹朝霞,李均,2017,内质网应激与肾脏纤维化,海南医学,28(4):615-617)
Chen N.Z.,Jiang C.,and Li X.K.,2016,Role of endoplasmic reticulum stress in diseases,Zhongguo Shengwu Gongcheng Zazhi(China Biotechnology),36(1):76-85(陈娜子,姜潮,李校堃,2016,内质网应激与疾病,中国生物工程杂志,36(1):76-85)
Chen S.S.,He Z.Z.,Jiang S.X.,Xing J.J.,Lv X.Y.,and Lan H.Y.,2014,Cloning and expression analysis of calcium-dependent phosphokinase genes in Chenopodium album under stresses,Zhiwu Xuebao(Chinese Bulletin of Botany),49(2):139-149(陈莎莎,贺转转,姜生秀,邢佳佳,吕秀云,兰海燕,2014,藜钙依赖磷酸激酶基因CaCPK的克隆及胁迫表达,植物学报,49(2):139-149)
Fu Y.,Li Y.,Yang F.W.,and Lin S.D.,2013,The molecular mechanism and significance of autophagy induced by endoplasmic reticulum stress,Xiandai Shengwu Yixue Jinzhan(Progress in Modern Biomedicine),13(12):2393-2397(付裕,李滢,杨方万,林世德,2013,内质网应激诱导自噬的分子机制及意义,现代生物医学进展,13(12):2393-2397)
Han D.,Lerner A.G.,Walle L.V.,Upton J.P.,Xu W.,Hagen A.,Backes B.J.,Oakes S.A.,and Papa F.R.,2009,IRE1αkinase activation mod es contro l alternate endoribonuclease outputs to determine divergent cell fates,Cell,138(3):562-575
Hu N.B.,Sui Y.H.,He K.Q.,Wang M.M.,Zhang R.N.,Hu X.X.and Han X.T.,2016,Study of polysaccharides,organic acid amino acid and its compound on copigmentation of leaf pigment in purple pepper,Jiyinzuxue Yu Yingyong Shengwuxue(Genomics and Applied Biology),36(3):715-720(胡能兵,隋益虎,何克勤,王蜜蜜,张若男,胡肖肖,韩小田2016,多糖、有机酸、氨基酸及其复配对紫色辣椒叶片色素辅色效果研究,基因组学与应用生物学,36(3):715-720)
Li X.C.,Fang L.,Li Z.J.,Devi P.N.,Chen F.,and Cai X.H.,2016Effect of endoplasmic reticulum stress in brain injury following chronic intermittent hypoxic in growing rats,Zhongguo Bingli Shengli Zazhi(Chinese Journal of Pathophysiology),32(8):1413-1418(李秀翠,方励,李志洁,POONITNeha Devi,陈帆,蔡晓红,2016,内质网应激在慢性间歇低氧幼鼠脑损害中的作用,中国病理生理杂志,32(8)1413-1418)
Lu S.J.,Yang Z.T.,Sun L.,Sun L.,Song Z.T.,and Liu J.X.2012,Conservation of IRE1 regulated bZIP74 m RNA unconventional splicing in rice(Oryza sativa L.)involved in ER stress responses,Mol.Plant,5(2):504-514
Ma T.,and Xue C.R.,2008,Endoplasmic reticulum stress and apoptosis,Yixue Zongshu(Medical Recapitulate),14(23):3565-3567(马涛,薛承锐,2008,内质网未折叠蛋白反应与凋亡信号机制研究进展,医学综述,14(23):3565-3567)
Mao T.,Yang L.,and Liu Y.,2011,Endoplasmic reticulum stress and metabolic dysfunction,Zhongguo Xibao Shengwuxue Xuebao(Chinese Journal of Cell Biology),33(7):727-737(毛婷,杨柳,刘勇,2011,细胞内质网应激与糖脂代谢紊乱的机制关联,中国细胞生物学学报,33(7):727-737)
Pan Y.J.,Wang Y.,Xu J.Q.,Wu J.F.,Yu S.Y.,Zeng G.F.,and Zhao G.J.,2016,Advance in the relationship between stero regulatory element-binding proteins and inflammation Shengwu Huaxue Yu Shengwu Wuli Jinzhan(Progress in Biochemistry and Biophysics),43(12):1146-1153(盘艳君王燕,徐健强,吴剑锋,喻思扬,曾高峰,赵国军,2016,固醇调节元件结合蛋白与炎症的关系研究进展,生物化学与生物物理进展,43(12):1146-1153)
Rui D.,Cui X.Z.,Ji W.Z.,Min J.J.,Ji Q.C.,and Ren J.L.,2014Expression and significance of unfolded protein response related factors(GRP78,ATF6 and XPB1)in human esophageal squamous cell carcinoma,Zhenduan Binglixue Zazhi(Chinese Journal of Diagnostic Pathology),21(5):293-296300(闰东,崔新征,吉文仲,闵建军,吉庆春,任景丽,2014未折叠蛋白反应相关因子GRP78、ATF6和XPB 1在人食管鳞状细胞癌中的表达及其意义,诊断病理学杂志,21(5):293-296,300)
Shaffer A.L.,Shapiro-Shelef M.,Iwakoshi N.N.,Lee A.H.,Qian S.B.,Zhao H.,Yu X.,Yang L.,Tan B.K.,Rosenwald A.,Hurt E.M.,Petroulakis E.,Sonenberg N.,Yewdell J.W.,Calame K.,Glimcher L.H.,and Staudt L.M.,2004,XBP1downstream of Blimp-1,expands the secretory apparatus and other organelles,and increases protein synthesis in plasma cell differentiation,Immunity,21(1):81-93
Song Y.,Yuan Y.Q.,and Yu J.,2013,Survery of study on endoplasmic reticulum stress perk apoptosis pathway,Zhonghua Zhongyiyao Xuekan(Chinese Archives of Traditional Chinese Medicine),31(5):1009-1011(宋洋,袁宜勤,郁洁,2013,内质网应激PERK凋亡通路研究进展,中华中医药学刊,31(5):1009-1011)
Su W.W.,Ding G.X.,Zhu C.H.,Yuan Y.G.,Zhang A.H.,and Huang S.M.,2011,Effect of knockdown of Sigma-1 receptor on endoplasmic reticulum stress and podocyte injury,Nanjin Yike Daxue Xuebao(Acta Universitatis Medicinalis Nanjing),31(5):667-672(苏维维,丁桂霞,朱春华,袁杨刚,张爱华,黄松明,2011,Sig-1R基因表达抑制对内质网应激和足细胞损伤的影响,南京医科大学学报,31(5):667-672)
Sun L.,Wang X.L.,Zhang Y.F.,Sun W.H.,Liu J.X.,and Song Z.T.,2018,The resistance analysis of Arabidopsis thaliana transcription factor NAC103 in the ER stress response,Fenzi Zhiwu Yuzhong(Molecular Plant Breedinge),16(5):1475-1481(孙玲,王晓蕾,张宇飞,孙卫红,刘建祥,宋泽婷,2018,拟南芥转录因子NAC103在内质网胁迫应答中的抗性分析,分子植物育种,16(5):1475-1481)
Wang H.,and Cai D.F.,2006,Ca2+and endoplasmic reticulum-induced apoptosis,Guoji Bingli Kexue Yu Linchuang Zazhi(International Journal of Pathology and Clinical Medicine),26(4):283-290(王虎,蔡定芳,2006,Ca2+与内质网途径的细胞凋亡,国际病理科学与临床杂志,26(4):283-290)
Wang W.D.,2017,Endoplasmic reticulum stress and kidney diseases,Zhongshan Daxue Xuebao(Journal of Sun Yat-sen University),38(2):196-203(王蔚东,2017,内质网应激与肾脏疾病,中山大学学报,38(2):196-203)
Wang Y.,Shen J.,Arenzana N.,Tirasophon W.,Kaufman R.J.,and Prywes R.,2000,Activation of ATF6 and an ATF6DNA binding site by the endoplasmic reticulum stress response,J.Biol.Chem.,275(35):27013-27020
Wei N.B.,Liu H.Y.,Wang H.F.,Ren D.X.,Liu J.X.,and Wang C.,2013,Research progress of mechanism of action of proteins in cholesterol metabolism of sterol regulatory element binding,Zhongguo Xumu Zazhi(Chinese Journal of Animal Science),49(5):80-84(魏宁波,刘红云,汪海峰,任大喜,刘建新,王翀,2013,固醇调控元件结合蛋白在胆固醇代谢中作用机制的研究进展,中国畜牧杂志,49(5):80-84)
Wu J.,and Zhang X.C.,2015,Research progress of UPR in hepatocellular carcinoma,Biaoji Mianyi Fenxi Yu Linchuang(Labeled Immunoassays and Clinical Medicine),22(3):233-236(吴健,张新晨,2015,未折叠蛋白反应在肝癌中的作用研究进展,标记免疫分析与临床,22(3):233-236)
Xia Y.N.,Li X.M.,Yuan N.N.,Zhang X.L.,and Tan Y.X.,2017Effect of hydrogen on endoplasmic reticulum stress and neural apoptosis in rats with cerebral ischemia-reperfusion injury,Chongqin Yiyuan(Chongqing Medicine),46(9):1159-1162,1167(夏裕宁,李雪梅,袁楠楠,张鑫磊,谭永星,2017氢气对大鼠局灶性脑缺血再灌注损伤内质网应激及神经细胞凋亡的影响,重庆医学,46(9):1159-1162,1167)
Xu M.,and Wang T.,2014,Endoplasmic reticulum stress and related molecular chaperones,Jiepou Xueke Jinzhan(Progress of Anatomical Sciences),20(4):381-384(徐盟,王涛,2014内质网应激反应与相关分子伴侣,解剖科学进展,20(4)381-384)
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