Linked Life Data

20497906

Source:http://linkedlifedata.com/resource/pubmed/id/20497906

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-8-6
pubmed:abstractText
Hyperglycemia (HG) significantly increases mortality after myocardial infarction (MI) in patients with and without established diabetes. The specific underlying mechanism remains unknown. The present study attempted to determine whether nitrative inactivation of thioredoxin-1 (Trx-1) may contribute to the exaggerated myocardial ischemia/reperfusion (I/R) injury observed in the hyperglycemic condition. Diabetes was induced by multiple intraperitoneal injections of low-dose streptozotocin (STZ) in mice. After 30 min ischemia by slip-knot ligature of the left anterior descending coronary artery, the myocardium was reperfused for 3h after knot release (for apoptosis, Trx-1-activity, and -nitration determination) or 24h (for cardiac function and infarct size determination). At 10 min before reperfusion, diabetic mice were randomized to receive vehicle, EUK134 (a peroxynitrite scavenger), recombinant human Trx-1 (rhTrx-1), or SIN-1 (a peroxynitrite donor) nitrated Trx-1 (N-Trx-1) administration. Diabetes intensified I/R-induced myocardial injury, evidenced by further enlarged infarct size, increased apoptosis, and decreased cardiac function in diabetic mice. Trx-1 nitrative inactivation was elevated in the diabetic heart before I/R and was further amplified after I/R. Treatment with EUK134 or rhTrx-1, but not N-Trx-1, before reperfusion significantly reduced Trx-1 nitration, preserved Trx-1 activity, attenuated apoptosis, reduced infarct size, and improved cardiac function in diabetic mice. Taken together, our results demonstrated that HG increased cardiac vulnerability to I/R injury by enhancing nitrative inactivation of Trx-1, suggesting that blockade of Trx-1 nitration, or supplementation of exogenous rhTrx-1, might represent novel therapies to attenuate cardiac injury after MI in diabetic patients.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1095-8584
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
354-61
pubmed:meshHeading
pubmed-meshheading:20497906-Animals, pubmed-meshheading:20497906-Apoptosis, pubmed-meshheading:20497906-Blood Glucose, pubmed-meshheading:20497906-Cells, Cultured, pubmed-meshheading:20497906-Diabetes Mellitus, Experimental, pubmed-meshheading:20497906-Diabetic Cardiomyopathies, pubmed-meshheading:20497906-Heart, pubmed-meshheading:20497906-Hyperglycemia, pubmed-meshheading:20497906-Immunoblotting, pubmed-meshheading:20497906-Immunoprecipitation, pubmed-meshheading:20497906-Mice, pubmed-meshheading:20497906-Myocardial Reperfusion Injury, pubmed-meshheading:20497906-Nitrates, pubmed-meshheading:20497906-Nitrosation, pubmed-meshheading:20497906-Peroxynitrous Acid, pubmed-meshheading:20497906-Thioredoxins, pubmed-meshheading:20497906-Tyrosine, pubmed-meshheading:20497906-p38 Mitogen-Activated Protein Kinases
pubmed:year
2010
pubmed:articleTitle
Nitrative inactivation of thioredoxin-1 increases vulnerability of diabetic hearts to ischemia/reperfusion injury.
pubmed:affiliation
Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't