Linked Life Data

18441519

Source:http://linkedlifedata.com/resource/pubmed/id/18441519

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-4-28
pubmed:abstractText
Cardiac tissues contain cells susceptible to and cells resistant to apoptosis, and this difference is important for normal morphogenesis during development and for abnormal loss of cells during pathogenesis such as myocardial infarction and heart failure. While efforts have been made to understand the cellular and intercellular events of apoptotic cells, the signaling mechanisms in cells surviving from apoptotic injuries have been overlooked. Understanding signal transduction processes in cells with apoptosis resistance is of crucial importance to develop better strategies of preserving post-mitotic cells. To this end, we performed studies in neonatal rat ventricular myocytes using oxidative stress (H(2)O(2)) as an apoptotic inducer. We identified a population of cells bearing higher resistance to apoptosis and found that the cells that survived from apoptotic insults had markedly higher levels of AKT and STAT3. Inhibition of AKT activity by a dominant negative AKT construct or by a PI3K inhibitor reduced active NF-kappaB and STAT3 expression without significantly altering the activity of the latter. Activation of AKT by a constitutively activated AKT construct caused the opposite effects. Direct activation of NF-kappaB also enhanced STAT3 expression, an effect abrogated by NF-kappaB inhibitor. On the other hand, knockdown of STAT3 by siRNA or inhibition of STAT3 activity by decoy oligodeoxynucleotides or by JAK2 inhibitor diminished AKT expression. In conclusion, cardiomyocytes possess an apoptosis-resistant property as a cytoprotection mechanism which is likely conferred by mutual transactivation between AKT/NF-kappaB and JAK2/STAT3, a novel crosstalk between the two signaling pathways within the networking governing the cell fate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1421-9778
pubmed:author
pubmed:copyrightInfo
(c) 2008 S. Karger AG, Basel
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
305-14
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
JAK/STAT and PI3K/AKT pathways form a mutual transactivation loop and afford resistance to oxidative stress-induced apoptosis in cardiomyocytes.
pubmed:affiliation
Department of Pharmacology (State-Province key lab of China), Harbin Medical University, Harbin, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't