Targeting endoplasmic reticulum stress in liver disease

References

• Anelli T, Sitia R. Protein quality control in the early secretory pathway. EMBO J. 2008;27(2):315–327.
   PubMed Web of Science ®Google Scholar
• Bertolotti A, Zhang Y, Hendershot LM, et al. Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2000;2(6):326–332.
   PubMed Web of Science ®Google Scholar
• Shen J, Chen X, Hendershot L, et al. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell. 2002;3(1):99–111.
   PubMed Web of Science ®Google Scholar
• Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059):1081–1086.
   PubMed Web of Science ®Google Scholar
• Malhotra JD, Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol. 2007;18(6):716–731.
   PubMed Web of Science ®Google Scholar
• Soboloff J, Rothberg BS, Madesh M, et al. STIM proteins: dynamic calcium signal transducers. Nat Rev Mol Cell Biol. 2012;13(9):549–565.
   PubMed Web of Science ®Google Scholar
• Oikawa D, Kimata Y, Kohno K, et al. Activation of mammalian IRE1alpha upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins. Exp Cell Res. 2009;315(15):2496–2504.
   PubMed Web of Science ®Google Scholar
• Novoa I, Zeng H, Harding HP, et al. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol. 2001;153(5):1011–1022.
   PubMed Web of Science ®Google Scholar
• Marciniak SJ, Yun CY, Oyadomari S, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004;18(24):3066–3077.
   PubMed Web of Science ®Google Scholar
• Urano F, Wang X, Bertolotti A, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 2000;287(5453):664–666.
   PubMed Web of Science ®Google Scholar
• Kim I, Shu CW, Xu W, et al. Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. J Biol Chem. 2009;284(3):1593–1603.
   PubMed Web of Science ®Google Scholar
• Han D, Lerner AG, Vande Walle L, et al. IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates. Cell. 2009;138(3):562–575.
   PubMed Web of Science ®Google Scholar
• Santos CXC, Tanaka LY, Wosniak J, et al. Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid Redox Signal. 2009;11(10):2409–2427.
   PubMed Web of Science ®Google Scholar
• Yamazaki H, Hiramatsu N, Hayakawa K, et al. Activation of the Akt-NF- B pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol. 2009;183(2):1480–1487.
   PubMed Web of Science ®Google Scholar
• Jiang HY, Wek SA, McGrath BC, et al. Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol Cell Biol. 2003;23(16):5651–5663.
   PubMed Web of Science ®Google Scholar
• Zhang K, Shen X, Wu J, et al. Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell. 2006;124(3):587–599.
   PubMed Web of Science ®Google Scholar
• Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012;13(2):89–102.
   PubMed Web of Science ®Google Scholar
• Dara L, Ji C, Kaplowitz N. The contribution of endoplasmic reticulum stress to liver diseases. Hepatology. 2011;53(5):1752–1763.
   PubMed Web of Science ®Google Scholar
• Ji C. Mechanisms of alcohol-induced endoplasmic reticulum stress and organ injuries. Biochem Res Int. 2012;2012:216450.
   PubMedGoogle Scholar
• Howarth DL, Vacaru AM, Tsedensodnom O, et al. Alcohol disrupts endoplasmic reticulum function and protein secretion in hepatocytes. Alcohol Clin Exp Res. 2012;36(1):14–23.
   PubMed Web of Science ®Google Scholar
• Longato L, Ripp K, Setshedi M, et al. Insulin resistance, ceramide accumulation, and endoplasmic reticulum stress in human chronic alcohol-related liver disease. Oxid Med Cell Longev. 2012;2012:479348.
   PubMed Web of Science ®Google Scholar
• Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 2004;11(4):381–389.
   PubMed Web of Science ®Google Scholar
• Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease. J Hepatol. 2011;54(4):795–809.
   PubMed Web of Science ®Google Scholar
• Werstuck GH, Lentz SR, Dayal S, et al. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest. 2001;107(10):1263–1273.
   PubMed Web of Science ®Google Scholar
• Esfandiari F, Villanueva JA, Wong DH, et al. Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005;289(1):G54–G63.
   PubMed Web of Science ®Google Scholar
• Ramirez T, Longato L, Dostalek M, et al. Insulin resistance, ceramide accumulation and endoplasmic reticulum stress in experimental chronic alcohol-induced steatohepatitis. Alcohol Alcohol. 2013;48(1):39–52.
   PubMed Web of Science ®Google Scholar
• Ji C, Kaplowitz N. Betaine decreases hyperhomocysteinemia, endoplasmic reticulum stress, and liver injury in alcohol-fed mice. Gastroenterology. 2003;124(5):1488–1499.
   PubMed Web of Science ®Google Scholar
• Ji C, Chan C, Kaplowitz N. Predominant role of sterol response element binding proteins (SREBP) lipogenic pathways in hepatic steatosis in the murine intragastric ethanol feeding model. J Hepatol. 2006;45(5):717–724.
   PubMed Web of Science ®Google Scholar
• Ji C, Kaplowitz N. ER stress: can the liver cope? J Hepatol. 2006;45(2):321–333.
   PubMed Web of Science ®Google Scholar
• Petrasek J, Iracheta-Vellve A, Csak T, et al. STING-IRF3 pathway links endoplasmic reticulum stress with hepatocyte apoptosis in early alcoholic liver disease. Proc Natl Acad Sci U S A. 2013;110(41):16544–16549.
   PubMed Web of Science ®Google Scholar
• Wang LR, Zhu GQ, Shi KQ, et al. Autophagy in ethanol-exposed liver disease. Expert Rev Gastroenterol Hepatol. 2015;9(8):1031–1037.
   PubMed Web of Science ®Google Scholar
• Hernandez-Gea V, Hilscher M, Rozenfeld R, et al. Endoplasmic reticulum stress induces fibrogenic activity in hepatic stellate cells through autophagy. J Hepatol. 2013;59(1):98–104.
   PubMed Web of Science ®Google Scholar
• Ying R, Wang XQ, Yang Y, et al. Hydrogen sulfide suppresses endoplasmic reticulum stress-induced endothelial-to-mesenchymal transition through Src pathway. Life Sci. 2016;144:208–217.
   PubMed Web of Science ®Google Scholar
• Puri P, Mirshahi F, Cheung O, et al. Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology. 2008;134(2):568–576.
   PubMed Web of Science ®Google Scholar
• Ozcan U, Cao Q, Yilmaz E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 2004;306(5695):457–461.
   PubMed Web of Science ®Google Scholar
• Gregor MF, Yang L, Fabbrini E, et al. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes. 2009;58(3):693–700.
   PubMed Web of Science ®Google Scholar
• Mosinski JD, Pagadala MR, Mulya A, et al. Gastric bypass surgery is protective from high-fat diet induced nonalcoholic fatty liver disease and hepatic endoplasmic reticulum stress. Acta Physiol. 2015. doi:10.1111/apha.12640. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Li JS, Wang WJ, Sun Y, et al. Ursolic acid inhibits the development of nonalcoholic fatty liver disease by attenuating endoplasmic reticulum stress. Food Funct. 2015;6(5):1643–1651.
   PubMed Web of Science ®Google Scholar
• Zhang N, Lu Y, Shen X, et al. Fenofibrate treatment attenuated chronic endoplasmic reticulum stress in the liver of nonalcoholic fatty liver disease mice. Pharmacology. 2015;95(3–4):173–180.
   PubMed Web of Science ®Google Scholar
• Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012;142(4):711–725.e6.
   Web of Science ®Google Scholar
• Sozio MS, Liangpunsakul S, Crabb D. The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Semin Liver Dis. 2010;30(4):378–390.
   PubMed Web of Science ®Google Scholar
• Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol. 2006;290(5):G852–G858.
   PubMed Web of Science ®Google Scholar
• Ji C, Shinohara M, Kuhlenkamp J, et al. Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes. Hepatology. 2007;46(5):1586–1596.
   PubMed Web of Science ®Google Scholar
• Bobrovnikova-Marjon E, Hatzivassiliou G, Grigoriadou C, et al. PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation. Proc Natl Acad Sci U S A. 2008;105(42):16314–16319.
   PubMed Web of Science ®Google Scholar
• Yoshiuchi K, Kaneto H, Matsuoka TA, et al. Direct monitoring of in vivo ER stress during the development of insulin resistance with ER stress-activated indicator transgenic mice. Biochem Biophys Res Commun. 2008;366(2):545–550.
   PubMed Web of Science ®Google Scholar
• Boden G, Duan X, Homko C, et al. Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes. 2008;57(9):2438–2444.
   PubMed Web of Science ®Google Scholar
• Lee AH, Scapa EF, Cohen DE, et al. Regulation of hepatic lipogenesis by the transcription factor XBP1. Science. 2008;320(5882):1492–1496.
   PubMed Web of Science ®Google Scholar
• Wang D, Wei Y, Pagliassotti MJ. Saturated fatty acids promote endoplasmic reticulum stress and liver injury in rats with hepatic steatosis. Endocrinology. 2006;147(2):943–951.
   PubMed Web of Science ®Google Scholar
• Yamamoto K, Takahara K, Oyadomari S, et al. Induction of liver steatosis and lipid droplet formation in ATF6alpha-knockout mice burdened with pharmacological endoplasmic reticulum stress. Mol Biol Cell. 2010;21(17):2975–2986.
   PubMed Web of Science ®Google Scholar
• Usui M, Yamaguchi S, Tanji Y, et al. Atf6alpha-null mice are glucose intolerant due to pancreatic beta-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance. Metabolism. 2012;61(8):1118–1128.
   PubMed Web of Science ®Google Scholar
• Kim KE, Kim H, Heo RW, et al. Myeloid-specific SIRT1 deletion aggravates hepatic inflammation and steatosis in high-fat diet-fed mice. Korean J Physiol Pharmacol. 2015;19(5):451–460.
   PubMed Web of Science ®Google Scholar
• Kammoun HL, Chabanon H, Hainault I, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009;119(5):1201–1215.
   PubMed Web of Science ®Google Scholar
• Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature. 2002;420(6913):333–336.
   PubMed Web of Science ®Google Scholar
• Du K, Herzig S, Kulkarni RN, et al. TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science. 2003;300(5625):1574–1577.
   PubMed Web of Science ®Google Scholar
• Nakae J, Biggs WH 3rd, Kitamura T, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet. 2002;32(2):245–253.
   PubMed Web of Science ®Google Scholar
• Liu WY, Xie DM, Zhu GQ, et al. Targeting fibroblast growth factor 19 in liver disease: a potential biomarker and therapeutic target. Expert Opin Ther Targets. 2015;19(5):675–685.
   PubMed Web of Science ®Google Scholar
• Liu WY, Huang S, Shi KQ, et al. The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target. Expert Opin Ther Targets. 2014;18(11):1305–1313.
   PubMed Web of Science ®Google Scholar
• Cheong H, Lee SS, Lee JS, et al. Phagocytic function of Kupffer cells in mouse nonalcoholic fatty liver disease models: evaluation with superparamagnetic iron oxide. J Magn Reson Imaging. 2015;41(5):1218–1227.
   PubMed Web of Science ®Google Scholar
• Feldman A, Aigner E, Weghuber D, et al. The potential role of iron and copper in pediatric obesity and nonalcoholic fatty liver disease. Biomed Res Int. 2015;2015:287401.
   PubMed Web of Science ®Google Scholar
• Okamoto K, Moriishi K, Miyamura T, et al. Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein. J Virol. 2004;78(12):6370–6380.
   PubMed Web of Science ®Google Scholar
• Awe K, Lambert C, Prange R. Mammalian BiP controls posttranslational ER translocation of the hepatitis B virus large envelope protein. FEBS Lett. 2008;582(21–22):3179–3184.
   PubMed Web of Science ®Google Scholar
• Sir D, Chen WL, Choi J, et al. Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology. 2008;48(4):1054–1061.
   PubMed Web of Science ®Google Scholar
• Wang HC, Wu HC, Chen CF, et al. Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Am J Pathol. 2003;163(6):2441–2449.
   PubMed Web of Science ®Google Scholar
• Li B, Gao B, Ye L, et al. Hepatitis B virus X protein (HBx) activates ATF6 and IRE1-XBP1 pathways of unfolded protein response. Virus Res. 2007;124(1–2):44–49.
   PubMed Web of Science ®Google Scholar
• Benali-Furet NL, Chami M, Houel L, et al. Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene. 2005;24(31):4921–4933.
   PubMed Web of Science ®Google Scholar
• Gong G, Waris G, Tanveer R, et al. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci U S A. 2001;98(17):9599–9604.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Gao B, Ye L, et al. Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response. J Microbiol. 2005;43(6):529–536.
   PubMed Web of Science ®Google Scholar
• Yeganeh B, Rezaei Moghadam A, Alizadeh J, et al. Hepatitis B and C virus-induced hepatitis: apoptosis, autophagy, and unfolded protein response. World J Gastroenterol. 2015;21(47):13225–13239.
   PubMed Web of Science ®Google Scholar
• Dreux M, Gastaminza P, Wieland SF, et al. The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci U S A. 2009;106(33):14046–14051.
   PubMed Web of Science ®Google Scholar
• Sir D, Kuo CF, Tian Y, et al. Replication of hepatitis C virus RNA on autophagosomal membranes. J Biol Chem. 2012;287(22):18036–18043.
   PubMed Web of Science ®Google Scholar
• Tanida I, Fukasawa M, Ueno T, et al. Knockdown of autophagy-related gene decreases the production of infectious hepatitis C virus particles. Autophagy. 2009;5(7):937–945.
   PubMed Web of Science ®Google Scholar
• Vescovo T, Refolo G, Romagnoli A, et al. Autophagy in HCV infection: keeping fat and inflammation at bay. Biomed Res Int. 2014;2014:265353.
   PubMed Web of Science ®Google Scholar
• Shrivastava S, Raychoudhuri A, Steele R, et al. Knockdown of autophagy enhances the innate immune response in hepatitis C virus-infected hepatocytes. Hepatology. 2011;53(2):406–414.
   PubMed Web of Science ®Google Scholar
• Gregoire IP, Rabourdin-Combe C, Faure M. Autophagy and RNA virus interactomes reveal IRGM as a common target. Autophagy. 2012;8(7):1136–1137.
   PubMed Web of Science ®Google Scholar
• Nagy G, Szarka A, Lotz G, et al. BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury. Toxicol Appl Pharmacol. 2010;243(1):96–103.
   PubMed Web of Science ®Google Scholar
• Lorz C, Justo P, Sanz A, et al. Paracetamol-induced renal tubular injury: a role for ER stress. J Am Soc Nephrol. 2004;15(2):380–389.
   PubMed Web of Science ®Google Scholar
• Nagy G, Kardon T, Wunderlich L, et al. Acetaminophen induces ER dependent signaling in mouse liver. Arch Biochem Biophys. 2007;459(2):273–279.
   PubMed Web of Science ®Google Scholar
• James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of acetaminophen-protein adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab Dispos. 2009;37(8):1779–1784.
   PubMed Web of Science ®Google Scholar
• Zhang J, Song S, Pang Q, et al. Corrigendum: serotonin deficiency exacerbates acetaminophen-induced liver toxicity in mice. Sci Rep. 2015;5:12184.
   PubMed Web of Science ®Google Scholar
• Wang X, Thomas B, Sachdeva R, et al. Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress. Proc Natl Acad Sci U S A. 2006;103(10):3604–3609.
   PubMed Web of Science ®Google Scholar
• Van den Hof WF, Van Summeren A, Lommen A, et al. Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity. Toxicology. 2014;324:18–26.
   PubMed Web of Science ®Google Scholar
• Chen L, Jarujaron S, Wu X, et al. HIV protease inhibitor lopinavir-induced TNF-alpha and IL-6 expression is coupled to the unfolded protein response and ERK signaling pathways in macrophages. Biochem Pharmacol. 2009;78(1):70–77.
   PubMed Web of Science ®Google Scholar
• Bochkis IM, Rubins NE, White P, et al. Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in endoplasmic reticulum stress. Nat Med. 2008;14(8):828–836.
   PubMed Web of Science ®Google Scholar
• Sasaki M, Yoshimura-Miyakoshi M, Sato Y, et al. A possible involvement of endoplasmic reticulum stress in biliary epithelial autophagy and senescence in primary biliary cirrhosis. J Gastroenterol. 2015;50(9):984–995.
   PubMed Web of Science ®Google Scholar
• Adachi T, Kaminaga T, Yasuda H, et al. The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury. J Clin Biochem Nutr. 2014;54(2):129–135.
   PubMed Web of Science ®Google Scholar
• Tamaki N, Hatano E, Taura K, et al. CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injury. Am J Physiol Gastrointest Liver Physiol. 2008;294(2):G498–505.
   PubMed Web of Science ®Google Scholar
• Mencin A, Seki E, Osawa Y, et al. Alpha-1 antitrypsin Z protein (PiZ) increases hepatic fibrosis in a murine model of cholestasis. Hepatology. 2007;46(5):1443–1452.
   PubMed Web of Science ®Google Scholar
• Borkham-Kamphorst E, Steffen BT, Van de Leur E, et al. CCN1/CYR61 overexpression in hepatic stellate cells induces ER stress-related apoptosis. Cell Signal. 2016;28(1):34–42.
   PubMed Web of Science ®Google Scholar
• Perlmutter DH, Silverman GA. Hepatic fibrosis and carcinogenesis in alpha1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders. Cold Spring Harb Perspect Biol. 2011;3(3):a005801.
   PubMed Web of Science ®Google Scholar
• Koo JH, Lee HJ, Kim W, et al. Endoplasmic reticulum stress in hepatic stellate cells promotes liver fibrosis via PERK-mediated degradation of HNRNPA1 and up-regulation of SMAD2. Gastroenterology. 2016;150(1):181–193.
   PubMed Web of Science ®Google Scholar
• Lim MP, Devi LA, Rozenfeld R. Cannabidiol causes activated hepatic stellate cell death through a mechanism of endoplasmic reticulum stress-induced apoptosis. Cell Death Dis. 2011;2:e170.
   PubMed Web of Science ®Google Scholar
• Jin L, Wang K, Liu H, et al. Genomewide histone H3 lysine 9 acetylation profiling in CD4+ T cells revealed endoplasmic reticulum stress deficiency in patients with acute-on-chronic liver failure. Scand J Immunol. 2015;82(5):452–459.
   PubMed Web of Science ®Google Scholar
• Maras JS, Maiwall R, Harsha HC, et al. Dysregulated iron homeostasis is strongly associated with multiorgan failure and early mortality in acute-on-chronic liver failure. Hepatology. 2015;61(4):1306–1320.
   PubMed Web of Science ®Google Scholar
• Ren F, Shi H, Zhang L, et al. The dysregulation of endoplasmic reticulum stress response in acute-on-chronic liver failure patients caused by acute exacerbation of chronic hepatitis B. J Viral Hepat. 2016;23(1):23–31.
   Web of Science ®Google Scholar
• Shuda M, Kondoh N, Imazeki N, et al. Activation of the ATF6, XBP1 and grp78 genes in human hepatocellular carcinoma: a possible involvement of the ER stress pathway in hepatocarcinogenesis. J Hepatol. 2003;38(5):605–614.
   PubMed Web of Science ®Google Scholar
• Jiang X, Kanda T, Nakamoto S, et al. Involvement of androgen receptor and glucose-regulated protein 78 kDa in human hepatocarcinogenesis. Exp Cell Res. 2014;323(2):326–336.
   PubMed Web of Science ®Google Scholar
• Romero-Ramirez L, Cao H, Nelson D, et al. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res. 2004;64(17):5943–5947.
   PubMed Web of Science ®Google Scholar
• Nakagawa H, Umemura A, Taniguchi K, et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 2014;26(3):331–343.
   PubMed Web of Science ®Google Scholar
• Wang X, Wang S, Liu Y, et al. The Hsp90 inhibitor SNX-2112 induces apoptosis of human hepatocellular carcinoma cells: the role of ER stress. Biochem Biophys Res Commun. 2014;446(1):160–166.
   PubMed Web of Science ®Google Scholar
• Fribley A, Wang CY. Proteasome inhibitor induces apoptosis through induction of endoplasmic reticulum stress. Cancer Biol Ther. 2006;5(7):745–748.
   PubMed Web of Science ®Google Scholar
• Jang MK, Han YR, Nam JS, et al. Protective effects of alisma orientale extract against hepatic steatosis via inhibition of endoplasmic reticulum stress. Int J Mol Sci. 2015;16(11):26151–26165.
   PubMed Web of Science ®Google Scholar
• Moon J, Koh SS, Malilas W, et al. Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress. Eur J Pharmacol. 2014;735:132–140.
   PubMed Web of Science ®Google Scholar
• Chen YJ, Su JH, Tsao CY, et al. Sinulariolide induced hepatocellular carcinoma apoptosis through activation of mitochondrial-related apoptotic and PERK/eIF2alpha/ATF4/CHOP pathway. Molecules. 2013;18(9):10146–10161.
   PubMed Web of Science ®Google Scholar
• Shimizu M, Morimoto H, Maruyama R, et al. Selective regulation of FGF19 and FGF21 expression by cellular and nutritional stress. J Nutr Sci Vitaminol. 2015;61(2):154–160.
   PubMed Web of Science ®Google Scholar
• Lin Z, Pan X, Wu F, et al. Fibroblast growth factor 21 prevents atherosclerosis by suppression of hepatic sterol regulatory element-binding protein-2 and induction of adiponectin in mice. Circulation. 2015;131(21):1861–1871.
   PubMed Web of Science ®Google Scholar
• Jiang S, Yan C, Fang QC, et al. Fibroblast growth factor 21 is regulated by the IRE1α-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis. J Biol Chem. 2014;289(43):29751–29765.
   PubMed Web of Science ®Google Scholar
• Hetz C, Chevet E, Harding HP. Targeting the unfolded protein response in disease. Nat Rev Drug Discov. 2013;12(9):703–719.
   PubMed Web of Science ®Google Scholar
• Kuo TF, Tatsukawa H, Matsuura T, et al. Free fatty acids induce transglutaminase 2-dependent apoptosis in hepatocytes via ER stress-stimulated PERK pathways. J Cell Physiol. 2012;227(3):1130–1137.
   PubMed Web of Science ®Google Scholar
• Yoshida H, Matsui T, Yamamoto A, et al. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107(7):881–891.
   PubMed Web of Science ®Google Scholar
• Volkmann K, Lucas JL, Vuga D, et al. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. J Biol Chem. 2011;286(14):12743–12755.
   PubMed Web of Science ®Google Scholar
• Mimura N, Fulciniti M, Gorgun G, et al. Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma. Blood. 2012;119(24):5772–5781.
   PubMed Web of Science ®Google Scholar
• Papandreou I, Denko NC, Olson M, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood. 2011;117(4):1311–1314.
   PubMed Web of Science ®Google Scholar
• Sanches M, Duffy NM, Talukdar M, et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. Nat Commun. 2014;5:4202.
   PubMed Web of Science ®Google Scholar
• Rahman FU, Ali A, Guo R, et al. Synthesis and anticancer activities of a novel class of mono- and di-metallic Pt(II)(salicylaldiminato)(DMSO or Picolino)Cl complexes. Dalton Trans. 2015;44(5):2166–2175.
   PubMed Web of Science ®Google Scholar
• Eletto D, Eletto D, Boyle S, et al. PDIA6 regulates insulin secretion by selectively inhibiting the RIDD activity of IRE1. FASEB J. 2016;30(2):653–665.
   PubMed Web of Science ®Google Scholar
• Fribley AM, Cruz PG, Miller JR, et al. Complementary cell-based high-throughput screens identify novel modulators of the unfolded protein response. J Biomol Screen. 2011;16(8):825–835.
   PubMed Web of Science ®Google Scholar
• Rojas C, Pan-Castillo B, Valls C, et al. Resveratrol enhances palmitate-induced ER stress and apoptosis in cancer cells. Plos One. 2014;9(12):e113929.
   PubMed Web of Science ®Google Scholar
• Tsukumo Y, Tomida A, Kitahara O, et al. Nucleobindin 1 controls the unfolded protein response by inhibiting ATF6 activation. J Biol Chem. 2007;282(40):29264–29272.
   PubMed Web of Science ®Google Scholar
• Tsukumo Y, Tsukahara S, Saito S, et al. A novel endoplasmic reticulum export signal: proline at the +2-position from the signal peptide cleavage site. J Biol Chem. 2009;284(40):27500–27510.
   PubMed Web of Science ®Google Scholar
• Choi JH, Choi AY, Yoon H, et al. Baicalein protects HT22 murine hippocampal neuronal cells against endoplasmic reticulum stress-induced apoptosis through inhibition of reactive oxygen species production and CHOP induction. Exp Mol Med. 2010;42(12):811–822.
   PubMed Web of Science ®Google Scholar
• Liu A, Wang W, Fang H, et al. Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice. Eur J Pharmacol. 2015;748:45–53.
   PubMed Web of Science ®Google Scholar
• Wang YF, Li T, Tang ZH, et al. Baicalein triggers autophagy and inhibits the protein kinase B/mammalian target of rapamycin pathway in hepatocellular carcinoma HepG2 cells. Phytother Res. 2015;29(5):674–679.
   PubMed Web of Science ®Google Scholar
• Yang J, Wang XY, Xue J, et al. Protective effect of apigenin on mouse acute liver injury induced by acetaminophen is associated with increment of hepatic glutathione reductase activity. Food Funct. 2013;4(6):939–943.
   PubMed Web of Science ®Google Scholar
• Shi T, Zhuang R, Zhou H, et al. [Effect of apigenin on protein expressions of PPARs in liver tissues of rats with nonalcoholic steatohepatitis]. Zhonghua Gan Zang Bing Za Zhi. 2015;23(2):124–129.
   PubMedGoogle Scholar
• Hu XY, Liang JY, Guo XJ, et al. 5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)-mediated apoptosis in hepatocellular carcinoma. Clin Exp Pharmacol Physiol. 2015;42(2):146–153.
   PubMed Web of Science ®Google Scholar
• Wong TY, Lin SM, Leung LK. The flavone apigenin blocks nuclear translocation of sterol regulatory element-binding protein-2 in the hepatic cells WRL-68. Br J Nutr. 2015;113(12):1844–1852.
   PubMed Web of Science ®Google Scholar
• Nakanishi T, Shimazawa M, Sugitani S, et al. Role of endoplasmic reticulum stress in light-induced photoreceptor degeneration in mice. J Neurochem. 2013;125(1):111–124.
   PubMed Web of Science ®Google Scholar
• Prachasilchai W, Sonoda H, Yokota-Ikeda N, et al. The protective effect of a newly developed molecular chaperone-inducer against mouse ischemic acute kidney injury. J Pharmacol Sci. 2009;109(2):311–314.
   PubMed Web of Science ®Google Scholar
• Hino S, Kondo S, Yoshinaga K, et al. Regulation of ER molecular chaperone prevents bone loss in a murine model for osteoporosis. J Bone Miner Metab. 2010;28(2):131–138.
   PubMed Web of Science ®Google Scholar
• Wang ZS, Lu FE, Xu LJ, et al. Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells. Acta Pharmacol Sin. 2010;31(5):578–584.
   PubMed Web of Science ®Google Scholar
• Li YP, Chen JJ, Shen JJ, et al. Synthesis and biological evaluation of geldanamycin analogs against human cancer cells. Cancer Chemother Pharmacol. 2015;75(4):773–782.
   PubMed Web of Science ®Google Scholar
• Ozcan U, Yilmaz E, Ozcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science. 2006;313(5790):1137–1140.
   PubMed Web of Science ®Google Scholar
• Vilatoba M, Eckstein C, Bilbao G, et al. Sodium 4-phenylbutyrate protects against liver ischemia reperfusion injury by inhibition of endoplasmic reticulum-stress mediated apoptosis. Surgery. 2005;138(2):342–351.
   PubMed Web of Science ®Google Scholar
• Vandewynckel YP, Laukens D, Devisscher L, et al. Tauroursodeoxycholic acid dampens oncogenic apoptosis induced by endoplasmic reticulum stress during hepatocarcinogen exposure. Oncotarget. 2015;6(29):28011–28025.
   PubMed Web of Science ®Google Scholar
• Suaud L, Miller K, Panichelli AE, et al. 4-Phenylbutyrate stimulates Hsp70 expression through the Elp2 component of elongator and STAT-3 in cystic fibrosis epithelial cells. J Biol Chem. 2011;286(52):45083–45092.
   PubMed Web of Science ®Google Scholar
• Cho EJ, Yoon JH, Kwak MS, et al. Tauroursodeoxycholic acid attenuates progression of steatohepatitis in mice fed a methionine-choline-deficient diet. Dig Dis Sci. 2014;59(7):1461–1474.
   PubMed Web of Science ®Google Scholar
• Ji X, Yao L, Wang M, et al. Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes. FEBS Lett. 2015;589(24 Pt B):3938–3944.
   PubMed Web of Science ®Google Scholar
• Song YF, Luo Z, Zhang LH, et al. Endoplasmic reticulum stress and disturbed calcium homeostasis are involved in copper-induced alteration in hepatic lipid metabolism in yellow catfish Pelteobagrus fulvidraco. Chemosphere. 2015;144:2443–2453.
   PubMed Web of Science ®Google Scholar
• Gani AR, Uppala JK, Ramaiah KVA. Tauroursodeoxycholic acid prevents stress induced aggregation of proteins in vitro and promotes PERK activation in HepG2 cells. Arch Biochem Biophys. 2015;568:8–15.
   PubMed Web of Science ®Google Scholar
• Yang L, Li P, Fu S, et al. Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance. Cell Metab. 2010;11(6):467–478.
   PubMed Web of Science ®Google Scholar
• Stocki P, Chapman DC, Beach LA, et al. Depletion of cyclophilins B and C leads to dysregulation of endoplasmic reticulum redox homeostasis. J Biol Chem. 2014;289(33):23086–23096.
   PubMed Web of Science ®Google Scholar
• Korolczuk A, Maciejewski M, Czechowska G, et al. Ultrastructural examination of renal tubular epithelial cells and hepatocytes in the course of chronic cyclosporin A treatment–a possible link to oxidative stress. Ultrastruct Pathol. 2013;37(5):332–339.
   PubMed Web of Science ®Google Scholar
• Zhou H, Zhu J, Yue S, et al. The dichotomy of endoplasmic reticulum stress response in liver ischemia-reperfusion injury. Transplantation. 2016;100(2):365–372.
   PubMed Web of Science ®Google Scholar
• Zhu J, Lu T, Yue S, et al. Rapamycin protection of livers from ischemia and reperfusion injury is dependent on both autophagy induction and mammalian target of rapamycin complex 2-Akt activation. Transplantation. 2015;99(1):48–55.
   PubMed Web of Science ®Google Scholar
• Wu JJ, Omar HA, Lee YR, et al. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms. Eur J Pharmacol. 2015;762:449–458.
   PubMed Web of Science ®Google Scholar
• San-Miguel B, Crespo I, Sanchez DI, et al. Melatonin inhibits autophagy and endoplasmic reticulum stress in mice with carbon tetrachloride-induced fibrosis. J Pineal Res. 2015;59(2):151–162.
   PubMed Web of Science ®Google Scholar
• Kim JS, Wang JH, Biel TG, et al. Carbamazepine suppresses calpain-mediated autophagy impairment after ischemia/reperfusion in mouse livers. Toxicol Appl Pharmacol. 2013;273(3):600–610.
   PubMed Web of Science ®Google Scholar
• Rutkowski DT, Wu J, Back SH, et al. UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Dev Cell. 2008;15(6):829–840.
   PubMed Web of Science ®Google Scholar
• Zinszner H, Kuroda M, Wang X, et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev. 1998;12(7):982–995.
   PubMed Web of Science ®Google Scholar
• Zhang K, Wong HN, Song B, et al. The unfolded protein response sensor IRE1alpha is required at 2 distinct steps in B cell lymphopoiesis. J Clin Invest. 2005;115(2):268–281.
   PubMed Web of Science ®Google Scholar
• Lee AH, Chu GC, Iwakoshi NN, et al. XBP-1 is required for biogenesis of cellular secretory machinery of exocrine glands. EMBO J. 2005;24(24):4368–4380.
   PubMed Web of Science ®Google Scholar