Linked Life Data

20097771

Source:http://linkedlifedata.com/resource/pubmed/id/20097771

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-3-22
pubmed:abstractText
Phosphoinositide 3-kinase (PI3K) mediates myocardium protective signaling through phosphorylation of phosphatidylinositol (Ptdins) to produce Ptdins(3,4,5)P(3). Lipid phosphatase and tensin homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating Ptdins(3,4,5)P(3); therefore, the inhibition of PTEN enhances PI3K/Akt signaling and could prevent myocardium from ischemia-reperfusion (I/R) injury. Here we studied 1) whether the pharmacological inhibition of PTEN by bisperoxovanadium molecules [BpV(HOpic)] attenuates simulated I/R (SIR) injury in vitro and 2) whether the administration of BpV(HOpic) either before or after ischemia limits myocardial infarct size (IS) and ameliorates cardiodysfunction caused by infarction. First, adult rat cardiomyocytes were treated with or without BpV(HOpic) and then exposure to SIR. Second, anesthetized rats received BpV(HOpic) either before or after ischemia. IS was assessed at 4 h reperfusion, and left ventricular function was evaluated by echocardiography at 28 days postreperfusion. As a result, BpV(HOpic) decreased cell death, improved 3-[4,5-yl]-2,5-diphenyltetrazolium bromide (MTT) viability, and reduced apoptosis in cells exposed to SIR. These protective effects of BpV(HOpic) are associated with increased phospho-Akt and the repression of caspase-3 activity. Second, the administration of BpV(HOpic) significantly reduced IS and suppressed caspase-3 activity following I/R injury and consequentially improved cardiac function at 28 day postinfarction. These beneficial effects of BpV(HOpic) are attributed to increases in myocardial levels of phosphorylation of Akt/endothelial nitric oxide synthase (eNOS), ERK-1/2, and calcium-dependent nitric oxide synthase activity. In conclusion, the pharmacological inhibition of PTEN protects against I/R injury through the upregulation of the PI3K/Akt/eNOS/ERK prosurvival pathway, suggesting a new therapeutic strategy to combat I/R injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
298
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1198-208
pubmed:meshHeading
pubmed-meshheading:20097771-Animals, pubmed-meshheading:20097771-Caspase 3, pubmed-meshheading:20097771-Cells, Cultured, pubmed-meshheading:20097771-Disease Models, Animal, pubmed-meshheading:20097771-Enzyme Inhibitors, pubmed-meshheading:20097771-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:20097771-Male, pubmed-meshheading:20097771-Myocardial Infarction, pubmed-meshheading:20097771-Myocardial Reperfusion Injury, pubmed-meshheading:20097771-Myocytes, Cardiac, pubmed-meshheading:20097771-Nitric Oxide Synthase Type III, pubmed-meshheading:20097771-PTEN Phosphohydrolase, pubmed-meshheading:20097771-Proto-Oncogene Proteins c-akt, pubmed-meshheading:20097771-Rats, pubmed-meshheading:20097771-Rats, Sprague-Dawley, pubmed-meshheading:20097771-Vanadium Compounds, pubmed-meshheading:20097771-Ventricular Dysfunction, Left, pubmed-meshheading:20097771-bcl-2-Associated X Protein
pubmed:year
2010
pubmed:articleTitle
Pharmacological inhibition of PTEN limits myocardial infarct size and improves left ventricular function postinfarction.
pubmed:affiliation
Dept. of Biochemistry and Molecular Biology, Univ. of Texas Medical Branch, Galveston, 77555, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't