Document Detail


Adenoviral gene transfer of hepatic stimulator substance confers resistance against hepatic ischemia-reperfusion injury by improving mitochondrial function.
MedLine Citation:
PMID:  23461564     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatic stimulator substance (HSS) has been suggested to protect liver cells from various toxins. However, the precise role of HSS in hepatic ischemia-reperfusion (I/R) injury remains unknown. This study aims to elucidate whether overexpression of HSS could attenuate hepatic ischemia-reperfusion injury and its possible mechanisms. Both in vivo hepatic I/R injury in mice and in vitro hypoxia-reoxygenation (H/R) in a cell model were used to evaluate the effect of HSS protection after adenoviral gene transfer. Moreover, a possible mitochondrial mechanism of HSS protection was investigated. Efficient transfer of the HSS gene into liver inhibited hepatic I/R injury in mice, as evidenced by improvement in liver function tests, the preservation of hepatic morphology, and a reduction in hepatocyte apoptosis. HSS overexpression also inhibited H/R-induced cell death, as detected by cell viability and cell apoptosis assays. The underlying mechanism of this hepatic protection might involve the attenuation of mitochondrial dysfunction and mitochondrial-dependent cell apoptosis, as shown by the good preservation of mitochondrial ultrastructure, mitochondrial membrane potential, and the inhibition of cytochrome c leakage and caspase activity. Moreover, the suppression of H/R-induced mitochondrial ROS production and the maintenance of mitochondrial respiratory chain complex activities may participate in this mechanism. This new function of HSS expands the possibility of its application for the prevention of I/R injury, such as hepatic resection and liver transplantation in clinical practice.
Authors:
Shu-Jun Jiang; Wen Li; Wei An
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human gene therapy     Volume:  24     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-19     Completed Date:  2014-02-18     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  443-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Animals
Apoptosis
Cell Survival
Humans
Liver / blood supply*,  metabolism
Male
Mice
Mitochondria, Liver / metabolism*
Peptides / genetics*,  metabolism
Reperfusion Injury / metabolism,  pathology,  therapy*
Transfection
Chemical
Reg. No./Substance:
0/Peptides; 0/hepatic stimulator substance
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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