Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice

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...

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Bibliographic Details
Published in:PloS one 2014-03, Vol.9 (3), p.e93304-e93304
Main Authors: Palanisamy, Arun P, Cheng, Gang, Sutter, Alton G, Liu, John, Lewin, David N, Chao, Julie, Chavin, Kenneth
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adenoviridae - genetics
Adenoviruses
Advertising executives
Alanine Transaminase - blood
Animals
Apoptosis
Aspartate Aminotransferases - blood
BAX protein
Biochemistry
Biology
Biology and Life Sciences
Cytochrome
Cytokines
Endothelium
Free radicals
Gene Expression
Humans
Injuries
Ischemia
Laboratories
Liver
Liver - enzymology
Liver - injuries
Liver - metabolism
Liver - pathology
Male
Medicine and Health Sciences
Mice
Mitochondria
Neutrophils
Nitration
Nitric oxide
Nitric Oxide Synthase Type III - genetics
Nitric-oxide synthase
Overexpression
p53 Protein
Proteins
Reperfusion
Reperfusion Injury - enzymology
Reperfusion Injury - genetics
Reperfusion Injury - metabolism
Reperfusion Injury - pathology
Respiration
Rodent control
Rodents
Surgery
Transplants & implants
Tumor proteins
Western blotting
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0093304