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The Nephroprotective Effect of TUDCA on Ischaemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Endoplasmic Reticulum Stress.
MedLine Citation:
PMID:  22212133     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 in AKI and to explore the exact mechanism, an ischaemia/reperfusion (I/R)-induced acute kidney injury (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 hr after ischaemia/reperfusion (I/R). GRP78 and CHOP expression and Caspase 12 activation were enhanced, reaching their peaks at 4 and 12 hr, respectively. TUDCA intervention not only decreased the renal tubular necrosis score and the cell apoptosis index but it 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.
Authors:
Xiang Gao; Lili Fu; Min Xiao; Chenggang Xu; Lijun Sun; Tong Zhang; Feng Zheng; Changlin Mei
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-28
Journal Detail:
Title:  Basic & clinical pharmacology & toxicology     Volume:  -     ISSN:  1742-7843     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101208422     Medline TA:  Basic Clin Pharmacol Toxicol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.
Affiliation:
Kidney institute of PLA, Department of Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China Department of Ultrasound, Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China Division of Experimental Diabetes and Aging, Department of Geriatrics, Mount Sinai School of Medicine, New York, USA.
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