CT-1 mediated cardioprotection against ischaemic re-oxygenation injury is mediated by PI3 kinase, Akt and MEK1/2 pathways.
Cardiotrophin-1 protects cardiac myocytes from ischaemic re-oxygenation (IR) injury. CT-1 activates MEK1/2,p42/44MAPK as well as the phosphatidylinositol (PI) 3-OH kinase (PI3) protein kinase B (PKB/Akt) pathway. In this study we investigate the signalling pathways that mediate the anti-apoptotic cell survival effect of CT-1 in IR. Dominant negative gene based inhibitors of MEK1/2, PI3-kinase and Akt inhibited CT-1 mediated cardioprotection in re-oxygenation as did chemical inhibitors of the PI3-kinase pathway. Hence the PI3-kinase/Akt pathway is required in addition to MEK1/2 to mediate CT-1 cardioprotection in IR.
Brar
B K
BK
Medical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London, WC1 1EH, UK.
Stephanou
A
A
Pennica
D
D
Latchman
D S
DS
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005799:Genes, Dominant; D020287:In Situ Nick-End Labeling; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D016207:Cytokines; D004791:Enzyme Inhibitors; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C092073:cardiotrophin 1; C494920:Akt1 protein, rat; C482127:Map2k1 protein, mouse