PDF下载 ( 1967 KB)
Endoplasmic reticulum stress signaling pathway and its association with liver diseases
-
摘要:
内质网应激(ERS)表现为内质网腔内错误折叠与未折叠蛋白聚集以及钙离子平衡紊乱,可激活未折叠蛋白反应、内质网超负荷反应和固醇调节级联反应等信号通路,既能引发糖调节蛋白GRP78、GRP94等内质网分子伴侣表达而产生保护效应,亦能诱导细胞凋亡。目前,关于ERS参与肝脏疾病的发生发展尚无系统性认识。综述了ERS相关信号通路的新进展及与其相关的部分肝脏疾病新进展,并对ERS介导的细胞凋亡及其在肝脏疾病中的作用进行阐述。干预ERS信号通路有望为未来肝脏疾病研究及治疗提供参考。
Abstract:Endoplasmic reticulum stress( ERS) manifests as the aggregation of misfolded and unfolded proteins in the endoplasmic reticulum lumen and disorder of calcium balance and can activate the signaling pathways involved in unfolded protein response,endoplasmic reticulum overload reaction,and sterol regulatory cascade response. ERS can not only exert a protective effect by inducing the expression of endoplasmic reticulum molecular chaperones such as glucose-regulated protein 78 and glucose-regulated protein 94,but also induce cell apoptosis.At present,there is still no systematic understanding of ERS involvement in the development and progression of liver diseases. This article summarizes the research advances in ERS-related signaling pathways and related liver diseases and elaborates on the role of ERS-mediated cell apoptosis in liver diseases. The intervention of ERS signaling pathways may provide a reference for the research and treatment of liver diseases in the future.
-
Key words:
- liver diseases /
- endoplasmic reticulum stress /
- signal transduction /
- apoptosis
-
[1] SO JS. Roles of endoplasmic reticulum stress in immune responses[J]. Mol Cells,2018,41(8):705-716. [2] YANG X,SRIVASTAVA R,HOWELL SH,et al. Activation of autophagy by unfolded proteins during endoplasmic reticulum stress[J]. Plant J,2016,85(1):83-95. [3] ZHENG Z,SHANG Y,TAO J. Endoplasmic reticulum stress signaling pathways:Activation and diseases[J]. Curr Protein Pept Sci,2019,20(9):935-943. [4] BERTOLOTTI A,ZhANG Y,HENDERSHOT LM,et al. Dynamic interaction of Bi P and ER stress transducers in the unfolded-protein response[J]. Nat Cell Biol,2000,2(6):326-332. [5] LI Y,ZHANG Y,FU H,et al. Hes1 knockdown exacerbates ischemic stroke following t MCAO by increasing ER stress-dependent apoptosis via the PERK/e IF2α/ATF4/CHOP signaling pathway[J]. Neurosci Bull,2019.[Epub ahead of print] [6] FUSAKIO ME,WILLY JA,WANG Y,et al. Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver[J]. Mol Biol Cell,2016,27(9):1536-1551. [7] TAN W,LIAO Y,QIU Y,et al. miRNA 146a promotes chemotherapy resistance in lung cancer cells by targeting DNA damage inducible transcript 3(CHOP)[J]. Cancer Lett,2018,428:55-68. [8] YOSHIDA H,MSTSUI T,YANAMOTO A,et al. RNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor[J]. Cell,2001,107(7):881-891. [9] KOH JH,WANG L,BEAUDOIN-CHABOT C. Lipid bilayer stress-activated IRE-1 modulates autophagy during endoplasmic reticulum stress[J]. J Cell Sci,2018,131(22):jcs217992. [10] COX JS,SHAMU CE,WALTER P. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase[J]. Cell,1993,73(6):1197-1206. [11] ZHANG SX,MA JH,BHATTA M,et al. The unfolded protein response in retinal vascular diseases:Implications and therapeutic potential beyond protein folding[J]. Prog Retin Eye Res,2015,45:111-131. [12] SHEN J,PRYWES R. Dependence of site-2 protease cleavage of ATF6 on prior site-1 protease digestion is determined by the size of the luminal domain of ATF6[J]. J Biol Chem,2004,279(41):43046-43051. [13] XU X,LEI T,LI W,et al. Enhanced cellular cholesterol efflux by naringenin is mediated through inhibiting endoplasmic reticulum stress-ATF6 activity in macrophages[J]. Biochim Biophys Acta Mol Cell Biol Lipids,2019,1864(10):1472-1482. [14] ZAMPINO R,BOEMIO A,SAGNELLI C,et al. Hepatitis B virus burden in developing countries[J]. World J Gastroenterol,2015,21(42):11941-11953. [15] POLLICINO T,AMADDEO G,RESTUCCIA A,et al. Impact of hepatitis B virus(HBV)preS/S genomic variability on HBV surface antigen and HBV DNA serum levels[J]. Hepatology,2012,56(2):434-443. [16] MONTALBANO R,HONRATH B,WISSNIOWSKI TT,et al. Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress:Involvement of cannabinoid axis in liver cancer cells[J]. Oncotarget,2016,7(15):20312-20323. [17] OU JH,RUTTER WJ. Regulation of secretion of the hepatitis B virus major surface antigen by the preS-1 protein[J]. J Virol,1987,61(3):782-786. [18] BOCK CT,TILLMANN HL,MANNS MP,et al. The pre-S region determines the intracellular localization and appearance of hepatitis B virus[J]. Hepatology,1999,30(2):517-525. [19] ZHANG XY,REN F. Role of endoplasmic reticulum stress in the pathogenesis of liver failure[J]. J Clin Hepatol,2019,35(9):1920-1923.(in Chinese)张向颖，任锋．内质网应激在肝衰竭发病机制中的作用[J]．临床肝胆病杂志，2019,35(9):1920-1923. [20] LEE HY,MARAHATTA A,BHANDARY B,et al. 4-phenylbutyric acid regulates CCl4-induced acute hepatic dyslipidemia in a mouse model:A mechanism-based PK/PD study[J].Eur J Pharmacol,2016,777:104-112. [21] CHEN L,REN F,ZHANG H,et al. Inhibition of glycogen synthase kinase 3βameliorates D-Gal N/LPS-induced liver injury by reducing endoplasmic reticulum stress-triggered apoptosis[J]. PLo S One,2012,7(9):e45202. [22] YIN C,CHEN C,HU J,et al. Inhibition effect of sorafenib combined with the saponin fraction from Gleditsia sinensis on H22 cells[J]. Central South Pharm,2019,17(5):676-681.(in Chinese)尹超，陈成，胡隽，等．猪牙皂皂苷通过内质网应激途径协同增强索拉非尼抗肝癌作用的研究[J]．中南药学，2019,17(5):676-681. [23] LIU J,FAN L,YU H,et al. Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages[J]. Hepatology,2019,70(1):241-258. [24] HUANG YF,ZHU DJ,CHEN XW,et al. Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway[J]. Oncotarget,2017,8(25):40264-40275. [25] FAN XL,ZHANG J,YU ZF,et al. Hinokitiol induces chondrosarcoma cell apoptosis through endoplasmic reticulum stress pathway[J]. J Oncol,2016,22(12):1020-1025.(in Chinese)范小良，张健，余泽锋，等．日柏醇通过内质网应激途径诱导软骨肉瘤细胞凋亡的体外研究[J]．肿瘤学杂志，2016,22(12):1020-1025. [26] JIN Y,ZHANG S,TAO R,et al. Oral exposure of mice to cadmium(Ⅱ)chromium(Ⅵ)and their mixture induce oxidative and endoplasmic reticulum stress mediated apoptosis in the livers[J]. Environ Toxicol,2016,31(6):693-705. [27] HUNG CS,LIN SF,LIU HH,et al. Survivin mediated therapeutic efficacy of gemcitabine through glucose-regulated protein 78 in hepatocellular carcinoma[J]. Ann Surg Oncol,2012,19(8):2744-2752. [28] GUO H,REN F,ZHANG L,et al. Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway[J]. Mol Med Rep,2016,13(3):2791-2800. [29] BRUNETTI E,KEM P,VUITTER DA,et al. Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans[J]. Acta Trop,2010,114(1):1-16. [30] NICOLAO MC,LOOS JA,RODRIGUEZ RODRIGUES C,et al.Bortezomib initiates endoplasmic reticulum stress,elicits autophagy and death in Echinococcus granulosus larval stage[J].PLo S One,2017,12(8):e0181528. [31] STADELMANN B,AESCHBACHER D,HUBER C,et al. Profound activity of the anti-cancer drug bortezomib against echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes[J]. PLo S Negl Trop Dis,2014,8(12):e3352. [32] de DIEGO JL,KATZ JM,MARSHALL P,et al. The ubiquitinproteasome pathway plays an essential role in proteolysis during Trypanosoma cruzi remodeling[J]. Biochemistry,2001,40(4):1053-1062. [33] YANG W,LI LG,LIU RD,et al. Molecular identification and characterization of Trichinella spiralis proteasome subunit beta type-7[J]. Parasit Vectors,2015,8:18. [34] MORI K. Signalling pathways in the unfolded protein response:Development from yeast to mammals[J]. J Biochem,2009,146(6):743-750. -
本文二维码
计量
- 文章访问数: 1454
- HTML全文浏览量: 50
- PDF下载量: 213
- 被引次数: 0
下载:
