Adenovirus-mediated ENOS Expression Augments Liver Injury After Ischemia/reperfusion in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Mar 27

PMID 24667691

Citations 8

Authors

Arun P Palanisamy

Gang Cheng

Alton G Sutter

John Liu

David N Lewin

Julie Chao

Kenneth Chavin

Affiliations

Soon will be listed here.

Abstract

Hepatic ischemia/reperfusion (l/R) injury continues to be a critical problem. The role of nitric oxide in liver I/R injury is still controversial. This study examines the effect of endothelial nitric oxide synthase (eNOS) over-expression on hepatic function following I/R. Adenovirus expressing human eNOS (Ad-eNOS) was administered by tail vein injection into C57BL/6 mice. Control mice received either adenovirus expressing LacZ or vehicle only. Sixty minutes of total hepatic ischemia was performed 3 days after adenovirus treatment, and mice were sacrificed after 6 or 24 hrs of reperfusion to assess hepatic injury. eNOS over expression caused increased liver injury as evidenced by elevated AST and ALT levels and decreased hepatic ATP content. While necrosis was not pervasive in any group, TUNEL demonstrated significantly increased apoptosis in Ad-eNOS infected livers. Western blotting demonstrated increased levels of protein nitration and upregulation of the pro-apoptotic proteins bax and p53. Our data suggest that over-expression of eNOS is detrimental in the setting of hepatic I/R.

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