Linked Life Data

16763164

Source:http://linkedlifedata.com/resource/pubmed/id/16763164

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-7-7
pubmed:abstractText
Previous studies indicate that endothelial nitric oxide synthase (eNOS) function is impaired in diabetes as a result of increased vascular generation of reactive oxygen species. We hypothesized that eNOS gene therapy would augment NO. bioavailability and protect against hepatic ischemia-reperfusion (I-R) injury in type 2 diabetes mellitus. We developed a transgenic (Tg) diabetic mouse in which eNOS is systemically overexpressed. We also examined the effects of hepatic eNOS adenovirus therapy in diabetic mice. Diabetic (db/db) and nondiabetic mice were subjected to hepatic I-R injury. In nondiabetic mice, genetic overexpression of eNOS (both eNOS-Tg and eNOS adenovirus) resulted in hepatoprotection. In contrast, hepatic I-R injury was significantly increased in the db/db eNOS-Tg mouse, as serum alanine aminotransaminase (ALT) levels were increased by 3.3-fold compared with diabetic controls. Similarly, eNOS adenovirus treatment resulted in a 3.2-fold increase in serum ALT levels as compared with diabetic controls. We determined that hepatic eNOS was dysfunctional in the db/db mouse and increased genetic expression of eNOS resulted in greater production of peroxynitrite. Treatment with the eNOS cofactor tetrahydrobiopterin (BH4) or the BH4 precursor sepiapterin resulted in a significant decrease in serum ALT levels following I-R injury. We present clear examples of the protective and injurious nature of NO. therapy in I-R. Our data indicate that eNOS exists in an "uncoupled" state in the setting of diabetes and that "recoupling" of the eNOS enzyme with cofactor therapy is beneficial.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
7
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
78-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16763164-Animals, pubmed-meshheading:16763164-Biological Availability, pubmed-meshheading:16763164-Biopterin, pubmed-meshheading:16763164-Diabetes Mellitus, Type 2, pubmed-meshheading:16763164-Drug Synergism, pubmed-meshheading:16763164-Gene Therapy, pubmed-meshheading:16763164-Liver, pubmed-meshheading:16763164-Metalloporphyrins, pubmed-meshheading:16763164-Mice, pubmed-meshheading:16763164-Mice, Inbred Strains, pubmed-meshheading:16763164-Mice, Transgenic, pubmed-meshheading:16763164-Nitric Oxide Donors, pubmed-meshheading:16763164-Nitric Oxide Synthase Type III, pubmed-meshheading:16763164-Nitrites, pubmed-meshheading:16763164-Phenotype, pubmed-meshheading:16763164-Phosphorylation, pubmed-meshheading:16763164-Pterins, pubmed-meshheading:16763164-Reperfusion Injury, pubmed-meshheading:16763164-Severity of Illness Index, pubmed-meshheading:16763164-Tyrosine
pubmed:year
2006
pubmed:articleTitle
eNOS gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes: a role for eNOS uncoupling.
pubmed:affiliation
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural