ISSN 1001-5256
CN 22-1108/R
Volume 35 Issue 12
Dec.  2019
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Article Contents

Effect of endoplasmic reticulum stress and autophagy on hepatocyte apoptosis

DOI: 10.3969/j.issn.1001-5256.2019.12.041
  • Received Date: 2019-07-08
  • Published Date: 2019-12-20
  • Endoplasmic reticulum stress and autophagy are two two-edged swords. On the one hand,in case of intracellular environment disturbance,unfolded protein response reduces protein synthesis,promotes protein degradation,and increases protein folding to restore intracellular homeostasis through three signaling pathways,while excessive stress activates a series of signaling molecules to induce apoptosis; on the other hand,autophagy is a protective pathway for self-degradation in human body and can absorb and decompose damaged or harmful macromolecular substances in cells through autophagic vacuole-lysosome complex and promote cell metabolism,while excessive autophagy also causes apoptosis. Endoplasmic reticulum stress and autophagy play important roles in the process of hepatocyte apoptosis. Therefore,these two molecular mechanisms may serve as targets for future drug research and provide therapeutic and diagnostic strategies for hepatocellular diseases.


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  • [1] FUJII J,HOMMA T,KOBAYASHI S,et al. Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease[J]. World J Biol Chem,2018,9(1):1-15.
    [2] KIM SY,KYAW YY,CHEONG J. Functional interaction of endoplasmic reticulum stress and hepatitis B virus in the pathogenesis of liver diseases[J]. World J Gastroenterol,2017,23(43):7657-7665.
    [3] MA LY,LI L,JIANG Y,et al. Study on Youchasaponin-induced apoptosis of HepG2 cells through the endoplasmic reticulum stress[J]. Chin Pharmacol Bull,2011,27(11):1523-1527.(in Chinese)马丽媛,李林,江玉,等.油茶皂苷通过内质网应激途径诱导人肝癌细胞HepG2凋亡的研究[J].中国药理学通报,2011,27(11):1523-1527.
    [4] ZHANG LP,MENG Y,YUAN XD,et al. Research progress of endoplasmic reticulum stress and apoptosis mediated signal transduction[J]. Biomed Eng Clin,2018,22(2):214-220.(in Chinese)张利平,孟燕,元小冬,等.内质网应激及介导细胞凋亡信号转导研究进展[J].生物医学工程与临床,2018,22(2):214-220.
    [5] WANG YZ,CHEN Y,YU L. The discovery and research of autophagy[J]. Chin J Biochem Mol Biol,2018,34(3):229-239.(in Chinese)王懿峥,陈扬,俞立.自噬的前世今生[J].中国生物化学与分子生物学报,2018,34(3):229-239.
    [6] FENG M,FU LL,ZHANG WH,et al. Endoplasmic reticulum stress regulates cell autophagy and apoptosis[J]. Chin J Cell Biol,2018,40(3):455-462.(in Chinese)丰梅,付凌玲,张伟华,等.内质网应激调控细胞自噬和凋亡[J].中国细胞生物学学报,2018,40(3):455-462.
    [7] WALLE LV,DANIEL JF,DEMON D,et al. Does caspase-12suppress inflammasome activation?[J]. Nature,2016,534(7605):e1-e4.
    [8] LI P,ZHOU LB,ZHAO T,et al. Caspase-9:Structure,mechanisms and clinical application[J]. Oncotarget,2017,8(14):23996-24008.
    [9] GU SY,CHEN CZ,JIANG XJ,et al. ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction underlie apoptosis induced by resveratrol and arsenic trioxide in A549cells[J]. Chem Biol Interact,2016,245:100-109.
    [10] LU M,LAWRENCE DA,MARSTERS S,et al. Opposing unfolded-protein-response signals converge on death receptor 5to control apoptosis[J]. Science,2014,345(6192):98-101.
    [11] TAMAKI T,KAMATSUKA K,SATO T,et al. A novel transmembrane protein defines the endoplasmic reticulum stressinduced cell death pathway[J]. Biochem Biophys Res Commun,2017,486(1):149-155.
    [12] SUN J,WANG W,TIAN Y,et al. Endoplasmic reticulum stress related reactive oxygen species and its mechanism[J]. China Med Herald,2018,15(16):42-44,54.(in Chinese)孙晶,王巍,田野,等.内质网应激相关活性氧及其机制[J].中国医药导报,2018,15(16):42-44,54.
    [13] YANG L,ZHU DX,HOU LD,et al. TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells[J]. Oncol Lett,2018,15(1):1343-1349.
    [14] SHIGEMI Z,MANABE K,HARA N,et al. Methylseleninic acid and sodium selenite induce severe ER stress and subsequent apoptosis through UPR activation in PEL cells[J]. Chem Biol Interact,2017,266:28-37.
    [15] KWAK GH,KIM HY. Msr B3 deficiency induces cancer cell apoptosis through p53-independent and ER stress-dependent pathways[J]. Arch Biochem Biophys,2017,621:1-5.
    [16] CADWELL K. Crosstalk between autophagy and inflammatory signalling pathways:Balancing defence and homeostasis[J].Nat Rev Immunol,2016,16(11):661-675.
    [17] THORBURN J,ANDRYSIK Z,STASKIEWICZ L,et al. Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels[J]. Cell Reports,2014,7(1):45-52.
    [18] DAI Y,GRANT S. BCL2L11/Bim as a dual-agent regulating autophagy and apoptosis in drug resistance[J]. Autophagy,2015,11(2):416-418.
    [19] BOOTH LA,TAVALLAI S,HAMED HA,et al. The role of cell signalling in the crosstalk between autophagy and apoptosis[J]. Cell Signal,2014,26(3):549-555.
    [20] BISCEGLIE F,ALINOVI R,PINELLI S,et al. Autophagy and apoptosis:Studies on the effects of bisthiosemicarbazone copper(ii)complexes on p53 and p53-null tumour cell lines[J]. Metallomics,2016,8(12):1255-1265.
    [21] FUJIWARA N,USUI T,OHAMA T,et al. Regulation of beclin1 phosphorylation and autophagy by PP2A and DAPK3[J]. J Biol Chem,2016,291(20):10858-10866.
    [22] LI JL,YE C,XIAO JG,et al. Effects of endoplasmic reticulum stress on autophagy and apoptosis of human leukemia cells via inhibition of the PI3K/AKT/m TOR signaling pathway[J].Mol Med Rep,2018,17(6):7886-7892.
    [23] WANG BD,LUO YK,ZHOU XS,et al. Trifluoperazine induces apoptosis through the upregulation of Bax/Bcl-2 and downregulated phosphorylation of AKT in mesangial cells and improves renal function in lupus nephritis mice[J]. Int J Mol Med,2018,41(6):3278-3286.
    [24] SHI XY,LIU YS,ZHANG YB,et al. Expression of PI3K/Akt pathway and related apoptotic proteinsinmouse braininduced by traumatic shock[J]. Traum Crit Med,2017,5(4):215-219.(in Chinese)史秀云,柳云思,张玉彪,等.小鼠脑爆震伤中PI3K/Akt通路及相关凋亡蛋白表达情况[J].创伤与急危重病医学,2017,5(4):215-219.
    [25] HART LS,CUNNINGHAM JT,DATTA T,et al. ER stress–mediated autophagy promotes Myc-dependent transformation and tumor growth[J]. J Clin Invest,2012,122(12):4621-4634.
    [26] LIU W,NING R,CHEN RN,et al. Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells[J]. Mol Carcinog,2016,55(5):440-457.
    [27] LI L,YIN HY,ZHAO Y,et al. Protective role of puerarin on LPS/D-Gal induced acute liver injury via restoring autophagy[J]. Am J Transl Res,2018,10(3):957-965.
    [28] LIU ZY,XIE ZQ. New regulatory effects of anti-apoptotic transcription factors in the pathogenesis of nonalcoholic fatty liver disease and hepatocellular carcinoma[J]. J Clin Hepatol,2019,35(2):375-375.(in Chinese)刘智勇,谢智钦.抗凋亡转录因子在非酒精性脂肪性肝病和肝细胞癌发病机制中的新调控作用[J].临床肝胆病杂志,2019,35(2):375-375.
    [29] REN LP,YU X,SONG GY,et al. Impact of activating transcription factor 4 signaling on lipogenesis in HepG2 cells[J].Mol Med Rep,2016,14(2):1649-1658.
    [30] WANG YL,ZHANG P,SU XL,et al. Establishment of a novel nonalcoholic fatty liver disease model using cholesterolfed rabbits with reference to the potential role of endoplasmic reticulum stress[J]. Mol Med Rep,2018,18(3):2898-2904.
    [31] YAN H,GAO YQ,ZHANG Y,et al. Chlorogenic acid alleviates autophagy and insulin resistance by suppressing JNK pathway in a rat model of nonalcoholic fatty liver disease[J]. J Biosci,2018,43(2):287-294.
    [32] LIU K,LOU JL,WEN T,et al. Depending on the stage of hepatosteatosis,p53 causes apoptosis primarily through either DRAM-induced autophagy or BAX[J]. Liver Int,2013,33(10):1566-1574.
    [33] MOREIRA AJ,ORDONEZ R,CERSKI CT,et al. Melatonin activates endoplasmic reticulum stress and apoptosis in rats with diethylnitrosamine-induced hepatocarcinogenesis[J]. PLo S One,2015,10(12):e0144517-e0144534.
    [34] GUO RJ. The mechanism of SENP1 affecting drug resistance in hepatocellular carcinoma[D]. Tianjin:Tianjin Medical University,2014.(in Chinese)郭瑞娟.SENP1在肝细胞肝癌耐药中的作用机制研究[D].天津:天津医科大学,2014.
    [35] SUN K,GUO XL,ZHAO QD,et al. Paradoxical role of autophagy in the dysplastic and tumor-forming stages of hepatocarcinoma development in rats[J]. Cell Death Dis,2013,4(2):e501.
    [36] LI RT. Effect of AZD5363 on apoptosis and autophagy in hepatocellular carcinoma cells[J]. Chin J Pathophysiol,2019,35(2):280-285.(in Chinese)李若彤.AZD5363诱导肝癌细胞凋亡与自噬的实验研究[J].中国病理生理杂志,2019,35(2):280-285.
    [37] KUNANOPPARAT A,KIMKONG I,PALAGA T,et al. Increased ATG5-ATG12 in hepatitis B virus-associated hepatocellular carcinoma and their role in apoptosis[J]. World J Gastroenterol,2016,22(37):8361-8374.
    [38] LI WM,YANG Q,MAO ZX. Signaling and induction of chaperone-mediated autophagy by the endoplasmic reticulum under stress conditions[J]. Autophagy,2018,14(6):1094-1096.
    [39] DANG ZF,DANG YM,CHEN C,et al. Emodin induces endoplasmic reticulum stress-associated apoptosis in hepatocellular carcinoma HepG2 cell line[J]. J Lanzhou Univ(Med Edition),2015,41(2):50-54.(in Chinese)党中峰,党雅梅,陈城,等.大黄素诱导对内质网应激相关蛋白表达及肝癌HepG2细胞凋亡的影响[J].兰州大学学报(医学版),2015,41(2):50-54.
    [40] SHAO FR,FANG ZQ. Effects of sophora capsule on acute tunicamycin-induced liver injury in mice[J]. Chin Clin Pharmacol Ther,2015,20(8):882-886.(in Chinese)邵芙蓉,方正清.苦参素胶囊对衣霉素诱导的小鼠急性肝损伤的保护作用[J].中国临床药理学与治疗学,2015,20(8):882-886.
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