title: Adenovirus-mediated eNOS expression augments liver injury after ischemia/reperfusion in mice.
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.
authors.affiliation: Division of Transplant Surgery, Department Of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Arun P
authors.initials: AP
authors.lastname: Palanisamy
authors.affiliation: Division of Transplant Surgery, Department Of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Division of Transplant Surgery, Department Of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Alton G
authors.initials: AG
authors.lastname: Sutter
authors.affiliation: Division of Transplant Surgery, Department Of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Liu
authors.affiliation: Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: David N
authors.initials: DN
authors.lastname: Lewin
authors.affiliation: Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Chao
authors.affiliation: Division of Transplant Surgery, Department Of Surgery, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Chavin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D015427:Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000255:Adenosine Triphosphate; D052250:Nitric Oxide Synthase Type III; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase