Linked Life Data

21421816

Source:http://linkedlifedata.com/resource/pubmed/id/21421816

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-6-2
pubmed:abstractText
AMPK activation during ischemia helps the myocardium to cope with the deficit of energy production. As AMPK activity is considered to be impaired in diabetes, we hypothesized that enhancing AMPK activation during ischemia above physiological levels would protect the ischemic diabetic heart through AMPK activation and subsequent inhibition of mitochondrial permeability transition pore (mPTP) opening. Isolated perfused hearts from normoglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (n ? 6/group) were subjected to 35 min of ischemia in the presence of 10, 20, and 40 ?M of A-769662, a known activator of AMPK, followed by 120 min of reperfusion with normal buffer. Myocardial infarction and AMPK phosphorylation were assessed. The effect of A-769662 on mPTP opening in adult cardiomyocytes isolated from both strains was also determined. A-769662 at 20 ?M reduced infarct size in both Wistar (30.5 ± 2.7 vs. 51.8 ± 3.9% vehicle; P < 0.001) and GK hearts (22.7 ± 3.0 vs. 48.5 ± 4.7% vehicle; P < 0.001). This protection was accompanied by a significant increase in AMPK and GSK-3? phosphorylation. In addition, A-769662 significantly inhibited mPTP opening in both Wistar and GK cardiomyocytes subjected to oxidative stress. We demonstrate that AMPK activation during ischemia via A-769662 reduces myocardial infarct size in both the nondiabetic and diabetic rat heart. Furthermore, this cardioprotective effect appears to be mediated through inhibition of mPTP opening. Our findings suggest that improving AMPK activation during ischemia can be another mechanism for protecting the ischemic heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2123-34
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:21421816-AMP-Activated Protein Kinases, pubmed-meshheading:21421816-Animals, pubmed-meshheading:21421816-Cells, Cultured, pubmed-meshheading:21421816-Diabetes Mellitus, pubmed-meshheading:21421816-Disease Models, Animal, pubmed-meshheading:21421816-Glycogen Synthase Kinase 3, pubmed-meshheading:21421816-Male, pubmed-meshheading:21421816-Microtubule-Associated Proteins, pubmed-meshheading:21421816-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:21421816-Myocardial Ischemia, pubmed-meshheading:21421816-Myocardial Reperfusion Injury, pubmed-meshheading:21421816-Myocytes, Cardiac, pubmed-meshheading:21421816-Phosphorylation, pubmed-meshheading:21421816-Pyrones, pubmed-meshheading:21421816-Rats, pubmed-meshheading:21421816-Rats, Inbred Strains, pubmed-meshheading:21421816-Rats, Wistar, pubmed-meshheading:21421816-Thiophenes
pubmed:year
2011
pubmed:articleTitle
Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury.
pubmed:affiliation
Hatter Cardiovascular Institute, Univ. College London Hospitals, 67 Chenies Mews, London, WC1E 6HX, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't