Linked Life Data

16284183

Source:http://linkedlifedata.com/resource/pubmed/id/16284183

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-12-12
pubmed:abstractText
Ischemic preconditioning (IPC), a brief period of ischemia and reperfusion (I/R), generates profound but transient protection against a subsequent prolonged ischemic episode. The serine-threonine kinase Akt has been shown to mediate IPC, and Akt activation is negatively regulated by the phosphatase PTEN, but whether PTEN activity is modulated by IPC has not been investigated. When isolated, perfused rat hearts were subjected to an IPC stimulus consisting of 15-minute ischemia and 30-minute reperfusion (I-15/R-30), PTEN protein levels and activity were decreased, and levels of phospho-AKT were increased, relative to nonischemic hearts. Hearts subjected to IPC demonstrated improved recovery of cardiac function when subsequently subjected to I-30/R-45 as compared with hearts subjected to I-30/R-45 without prior IPC. When hearts were subjected to I-15 followed by R-30, R-60, or R-120, PTEN reaccumulated gradually and its activity was restored. Phospho-Akt levels at R-120 were decreased and these hearts were no longer protected against injury when subjected to I-30/R-45. Wortmannin administration during reperfusion blocked Akt activation and PTEN reaccumulation. In ischemic hearts, PTEN was rapidly degraded. Pretreatment with proteasome inhibitor MG132 blocked ischemia-induced degradation of PTEN and blocked IPC. Reperfusion following I-15 induced oxidation of the remaining PTEN, leading to Akt activation. Perfusion of H2(O2) was sufficient to induce Akt activation. Thus, loss of PTEN activity leads to induction of IPC and feedback mechanisms designed to ensure that Akt activation is transient are responsible for decay of IPC.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
97
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1351-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
PTEN activity is modulated during ischemia and reperfusion: involvement in the induction and decay of preconditioning.
pubmed:affiliation
Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. czheqin1@jhmi.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural