内质网应激诱导未折叠蛋白反应干预药物作用研究进展

doi:10.3969/j.issn.1672-5069.2015.01.027

Abstract

Abstract: Endoplasmic reticulum（ER） homeostasis is perturbed by various pathological conditions,and a given new synthesized unfolded proteins might accumulate in the ER and result in endoplasmic reticulum stress（ERS）. ERS is related to the pathogenesis of the various liver diseases,and some scholars believe that the intervention of ERS will provide new choices for prevention and treatment of liver diseases. This paper will review the unfolded protein response due to ERS,which might be the target for medical intervention for liver diseases.

Key words: Endoplasmic reticulum stress, Unfolded protein response, Inhibitor, Gene therapy

Guo Yuanyuan, Ren Feng, Duan Zhongping, et al. Endoplasmic reticulum stress-induced unfolded protein response in medicine[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(1): 92-96.

References

[1] Walter P,Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science,2011,334（6059）:1081-1086.
[2] Ron D,Walter P. Signal integration in 9the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol,2007, （87）:519-529.
[3] Todd DJ,Lee AH,Glimcher LH. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol,2008,8（9）:663-674.
[4] Zhao LH,Ackerman SL. Endoplasmic reticulum stress in health and disease. Curr Opin Cell Biol,2006,18（4）:444-452.
[5] Rao RV,Hermel E,Castro-Obregon S,et al. Coupling endoplasmic reticulum stress to the cell death program. Biol Chem,2001,276（36）:33869-33874.
[6] Calfon M,Zeng H,Urano F,et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature,2002,420（6912）:202.
[7] Lee K,Tirasophon W,Shen X,et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev,2002,16（4）:452-466.
[8] Yoshida H,Matsui T,Yamamoto A,et al. XBP1mRNA 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.
[9] Acosta-Alvear D,Zhou Y,Blais A,et al. XBP1 controls diverse cell type-and condition-specific transcriptional regulatory networks. Mol Cell,2007,27（1）:53-66.
[10] Lee AH,Iwakoshi NN,Glimcher LH. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol Cell Bio1,2003,23（21）:7448-7459.
[11] 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.
[12] Nishitoh H,Matsuzawa A,Tobiume K. et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev,2002,16（11）:1345-1355.
[13] Upton JP,Wang L,Han D,et al. IRE1αcleaves select microRNAs during ER stress to derepress translation of proapoptotic caspase-2. Science,2012,338（6108）:818-822.
[14] Harding HP,Zhang Y,Zheng H,et al. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell,2003,11（3）:619-633.
[15] Lange PS,Chavez JC,Pinto JT,et al. ATF4 is an oxidative stress-inducible,prodeath transcription factor in neurons in vitro and in vivo. Exp Med,2008,205（5）:1227-1242.
[16] Novoa I,Zeng H,Harding HP. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α.Cell Biol,2001,153（5）:1011-1022.
[17] Tsaytler P,Harding HP,Ron D,et al. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science,2011,332（6025）:91-94.
[18] Schindler AJ,Schekman R.In vitro reconstitution of ER-stress induced ATF6 transport in COPII vesicles. Proc Natl Acad Sci USA,2009,106（42）:17775-17780.
[19] Haze K,Yoshida H,Yanagi H,et al. Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell,1999,10（11）:3787-3799.
[20] Ye J,Rwson RB,Komuro R,et.al. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol Cell,2000,6（6）:1355-1364.
[21] Hetz C,Chevet E,Harding HP. Targeting the unfolded protein response in disease. Natrue Reviews,2013,9（12）:703-718.
[22] 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.
[23] Ozcan L,Ergin AS,Lu A,et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab,2009,9（1）:35-51.
[24] Xiao C,Giacca A,Lewis GF. Sodium phenylbutyrate,a drug with known capacity to reduce endoplasmic reticulum stress,partially alleviates lipidinduced insulin resistance and β-cell dysfunction in humans. Diabetes,2011,60（3）:918-924.
[25] Kars M,Yang L,Gregor MF,et al. Tauroursodeoxycholic acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes,2010,59（8）:1899-1905.
[26] Ben M,Alfany F,Martel C,et al. Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion. Cell Death Dis,2010,1（7）:e52.
[27] Qi X,Hosoi T,Okuma Y,et al. Sodium 4-phenylbutyrate protects against cerebral ischemic injury. Mol. Pharmacol,2004,66（4）:899-908.
[28] Cross BC, Bond PJ, Sadowski PG,et al. The molecular basis for selective inhibition of unconventional mRNA splicing by an IRE1-binding small molecule. Proc Natl Acad Sci USA,2012,109（15）:E869-E878.
[29] Mimura N,Fulciniti M,Gorgun G,et al. Blockade of XBP1 splicing by inhibition of IRE1αis a promising therapeutic option in multiple myeloma. Blood,2012,119（24）:5772-5781.
[30] Papandreou I,Denko NC,Olson M,et al. Identification of an IRE1αendonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood,2011,117（4）:1311-1314.
[31] Volkmann K,Lucas JL,Vuga D,et al. Potent and selective inhibitors of the inositol-requiring enzyme 1 endoribonuclease. Biol Chem,2011,286（14）:12743-12755.
[32] Ri M,Tashiro E,Oikawa d,et al. Identification of toyocamycin, an agent cytotoxic for multiple myeloma cells,as a potent inhibitor of ER stress-induced XBP1mRNA splicing. Blood Cancer,2012,2（7）:e79.
[33] Ali MMU,Bagratuni T,Davenport EL,et al. Structure of the Ire1 autophosphorylation complex and implications for theunfolded protein response. EMBO,2011,30（5）:894-905.
[34] Bouchecareilh M,Higa A,Fribourg S,et al. Peptides derived from the bifunctional kinase/RNase enzyme IRE1αmodulate IRE1αactivity and protect cells from endoplasmic reticulum stress. FASEB,2011,25（9）:3115-3129.
[35] Axten JM,Medina JR,Feng YH,et al. Discoveryof7- methyl-5- （1-{[3-（trifluoromethyl）phenyl]acetyl}- 2,3-dihydro-1H-indol-5-yl）-7H-p yrrolo[2,3-d]pyrimidin-4-amine（GSK2606414）,a potent and selective first-in-class inhibitor of protein kinase R（PKR）-like endoplasmic reticulum kinase（PERK）. Med Chem,2012,55（7）:7193-7207.
[36] Atkins C,Liu Q,Minthorn E,et al. Characterization of a novel PERK kinase inhibitor with anti-tumor and anti-angiogenic activity. Cancer Res,2013,73（6）:1993-2002.
[37] Sidrauski C,Acosta AD,Khoutorsky A,et al. Pharmacological brake-release of mRNA translation enhances cognitive memory. Elife,2013,2:e00498.
[38] Costa MM,Sossin WS,Klann,E,et al. Translational control of long-lasting synaptic plasticity and memmory. Neuron,2009,61（1）:10-26.
[39] Chou TF,Brown SJ,Minond D,et al. Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways. Proc Natl Acad Sci USA,2011,108（3）:4834-4839.
[40] Polucci P,Magnaghi P,Angiolini M,et al. Alkylsulfanyl-1,2, 4-triazoles,a new class of allosteric valosine containing protein inhibitors. Med Chem,2013,56（2）:437-450.
[41] Witt J,Marks WJ Jr. An update on gene therapy in Parkinson’s disease. Curr Neurol Neurosci Rep,2011,11（4）362-370.
[42] Gorbatyuk MS,Knox T,Lavail MM,et al. Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci USA,2010,107（13）:5961-5966.
[43] Hu Y,Park KK,Yang L,et al. Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron,2012,73（3）:445-452.
[44] Gorbatyuk MS,Shabashvili A,Chen W,et al. Glucose regulated protein 78 diminishes α-synuclein neurotoxicity in a rat model of Parkinson disease. Mol Ther,2012,20（7）:1327-1337.
[45] Sado M,Yamasaki Y,Iwanaga T,et al. Protective effect against Parkinson’s disease-related insults through the activation of XBP1. Brain Res,2009,1257:16-24.
[46] Moreno JA,Radford H,Peretti D,et al. Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature, 2012, 485（7399）:507-511.

Endoplasmic reticulum stress-induced unfolded protein response in medicine

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Yan Ruibin, Ma Shumei, Zhuo Ma, et al. Significance of portal vain parameters by ultrasonography and serum MMP-2 and TIMP-2 detection in evaluation of liver fibrosis in patients with chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(4): 506-509.
[2]	Pan Gaofeng, Fu Maoying, Gao Yufeng.. Endoplasmic reticulum stress in pathogenesis of hepatic fibrosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(6): 987-990.
[3]	Wang Wei, Wang Huifang, Zhai Jingming, et al. Plasma SPINK1 levels in patients with hepatocellular carcinoma and its relationship with prognosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 525-528.
[4]	Wang Lan, Yang Yunmei. Role of glucose regulated protein 78 in the pathogenesis of nonalcoholic fatty liver disease [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(2): 309-312.
[5]	Ou Zhitao, Zhan Yuanjing, Guo Jiawei, et al. Effect of CIAPIN1 on proliferation and cell cycle of HegG2 cells in vitro [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(1): 38-41.
[6]	Sun Xiao, Yin Zhongpu, Yin Hongmei. Effects of tetramethylpyrazine on invasion and migration of HepG-2 cells in vitro [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(1): 118-120.
[7]	Chen Qian, Jiao Fangzhou, Zhang Haiyue. Protective effect of histone deacetylase inhibitor ACY1215 on hepatocyte mitochondria in rats with acute hepatic failure [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(6): 672-675.
[8]	Ge Hongyan，Jiang Hao.. Effect of Qinggan Jiuweisan，a Mongolia herbal medicine，on serum TIMP-1 levels in treatment of patients with alcoholic hepatitis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2016, 19(6): 720-721.
[9]	Cui Hongli, Yang Jun, Xiao Xiao, et al.. Clinical evaluation of recombinant adenovirus p53 therapy in combination with transcatheter arterial chemoembolization for patients with primary liver cancer [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(3): 237-240.
[10]	Pan Gaofeng, Gao Yufeng, Ye Jiaojiao, et al.. Peripheral leukocyte GRP78,CHOP and XBP1 mRNA levels in patients with chronic hepatitis B viral infection [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(2): 136-140.
[11]	Li Ziqiong, Mu Nila, Gao Feng. Inhibiting effects of antisense transforming growth factor β type I receptor and antisense TIMP-1 on experimental hepatic fibrosis in rats [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(1): 67-70.
[12]	Li Caidong, Yang Yongwei, Tian Pengfei, et al. Changes of serum macrophage migration inhibitory factor, IL-17 and IL-10 levels in patients with chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(1): 71-73.
[13]	Zhu Chuanlong, Li Yuwen, Li Wenting. Clinical significance of tissue inhibitor of metalloproteinases-1 in livers of patients with chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2014, 17(3): 245-249.
[14]	Wang Ming, Guo Jianwen, Xi Dong, et al.. Distribution and expression of adenovirus vector in mice with MHV-3-induced fulminant hepatitis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2012, 15(3): 216-219.
[15]	JIANG Yufeng，HUANG Fei，ZHANG Jianjun，et al.. RNA interference targets on connective tissue growth factor and tissue inhibitor of metalloproteinase-1 in vitro [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2011, 14(4): 246-248.