The Nephroprotective Effect of Tauroursodeoxycholic Acid on Ischaemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress

被引：70

作者：

Gao, Xiang ^{[1
]}

Fu, Lili ^{[1
]}

Xiao, Min ^{[1
,2
]}

Xu, Chenggang ^{[1
]}

Sun, Lijun ^{[1
]}

Zhang, Tong ^{[1
]}

Zheng, Feng ^{[3
]}

Mei, Changlin ^{[1
]}

机构：

[1] Second Mil Med Univ, Kidney Inst PLA, Dept Med, Changzheng Hosp, Shanghai 200003, Peoples R China

[2] Second Mil Med Univ, Dept Ultrasound, Changhai Hosp, Shanghai 200003, Peoples R China

[3] Mt Sinai Sch Med, Dept Geriatr, Div Expt Diabet & Aging, New York, NY USA

来源：

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY | 2012年 / 111卷 / 01期

基金：

中国国家自然科学基金;

关键词：

UNFOLDED PROTEIN RESPONSE; PRIMARY BILIARY-CIRRHOSIS; ER STRESS; ERYTHROPOIETIN PROTECTS; URSODEOXYCHOLIC ACID; RENAL-FAILURE; RAT-KIDNEY; APOPTOSIS; TRANSCRIPTION; CHOP;

D O I：

10.1111/j.1742-7843.2011.00854.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The incidence of acute kidney injury (AKI) is very high, and multiple physiopathological processes are involved, including endoplasmic reticulum stress (ERS). Tauroursodeoxycholic acid (TUDCA) is an endogenous bile acid derivative that has been reported to inhibit ERS. To determine whether TUDCA had a nephroprotective effect on AKI and to explore the exact mechanism, an ischaemia/reperfusion (I/R)-induced AKI mouse model and a tunicamycin-pre-treated TCMK-1 cell model were established. It was found that the renal tubular necrosis score and cell apoptosis index reached their peak 24 similar to hr after I/R. GRP78 and C/EBP homologous protein (CHOP) expression and Caspase 12 activation were enhanced, reaching their peaks at 4 and 12 similar to hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but also down-regulated GRP78 and CHOP expression and Caspase 12 activation. The survival rate of TCMK-1 cells pre-treated with TUDCA was significantly higher than that of TCMK-1 cells without TUDCA pre-treatment. In conclusion, TUDCA had a nephroprotective effect on IR-induced AKI by inhibiting ERS and by blocking GRP78 and CHOP expression, reducing Caspase 12 activation and inhibiting cell apoptosis.

引用

页码：14 / 23

页数：10

共 37 条

[1] Bile acids: regulation of apoptosis by ursodeoxycholic acid [J].

Amaral, Joana D. ;

Viana, Ricardo J. S. ;

Ramalho, Rita M. ;

Steer, Clifford J. ;

Rodrigues, Cecilia M. P. .

JOURNAL OF LIPID RESEARCH, 2009, 50 (09) :1721-1734

[2] Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group [J].

Bellomo, R ;

Ronco, C ;

Kellum, JA ;

Mehta, RL ;

Palevsky, P .

CRITICAL CARE, 2004, 8 (04) :R204-R212

[3] Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion [J].

Ben Mosbah, I. ;

Alfany-Fernandez, I. ;

Martel, C. ;

Zaouali, M. A. ;

Bintanel-Morcillo, M. ;

Rimola, A. ;

Rodes, J. ;

Brenner, C. ;

Rosello-Catafau, J. ;

Peralta, C. .

CELL DEATH & DISEASE, 2010, 1 :e52-e52

[4] Intracellular signaling by the unfolded protein response [J].

Bernales, Sebastian ;

Papa, Feroz R. ;

Walter, Peter .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2006, 22 :487-508

[5] Molecular Symbiosis of CHOP and C/EBPβ Isoform LIP Contributes to Endoplasmic Reticulum Stress-Induced Apoptosis [J].

Chiribau, Calin-Bogdan ;

Gaccioli, Francesca ;

Huang, Charlie C. ;

Yuan, Celvie L. ;

Hatzoglou, Maria .

MOLECULAR AND CELLULAR BIOLOGY, 2010, 30 (14) :3722-3731

[6] Chemical chaperones reduce endoplasmic reticulum stress and prevent mutant HFE aggregate formation [J].

de Almeida, Srgio F. ;

Picarote, Goncalo ;

Fleming, John V. ;

Carmo-Fonseca, Maria ;

Azevedo, Jorge E. ;

de Sousa, Maria .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (38) :27905-27912

[7] Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis [J].

Deniaud, A. ;

el dein, O. Sharaf ;

Maillier, E. ;

Poncet, D. ;

Kroemer, G. ;

Lemaire, C. ;

Brenner, C. .

ONCOGENE, 2008, 27 (03) :285-299

[8] Update on mechanisms of ischemic acute kidney injury [J].

Devarajan, Prasad .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (06) :1503-1520

[9] Perk is essential for translational regulation and cell survival during the unfolded protein response [J].

Harding, HP ;

Zhang, YH ;

Bertolotti, A ;

Zeng, HQ ;

Ron, D .

MOLECULAR CELL, 2000, 5 (05) :897-904

[10] Regulated translation initiation controls stress-induced gene expression in mammalian cells [J].

Harding, HP ;

Novoa, I ;

Zhang, YH ;

Zeng, HQ ;

Wek, R ;

Schapira, M ;

Ron, D .

MOLECULAR CELL, 2000, 6 (05) :1099-1108

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