Role of reactive oxygen species and phosphatidylinositol 3-kinase in cardiomyocyte differentiation of embryonic stem cells.
Cardiotypic development in embryonic stem cell-derived embryoid bodies may be regulated by reactive oxygen species (ROS). ROS were generated by a NADPH oxidase-like enzyme which was transiently expressed during the time course of embryoid body development. Incubation with either H(2)O(2) or menadione enhanced cardiomyogenesis, whereas the radical scavengers trolox, pyrrolidinedithiocarbamate and N-acetylcysteine exerted inhibitory effects. The phosphatidylinositol 3-kinase (PI-3-kinase) inhibitors LY294002 and wortmannin abolished cardiac commitment and downregulated ROS in embryoid bodies. Coadministration of LY294002 with prooxidants resumed cardiomyocyte differentiation, indicating a role for PI-3-kinase in the regulation of the intracellular redox state.
Sauer
H
H
Department of Neurophysiology, University of Cologne, Robert-Koch-Str. 39, D-50931, Cologne, Germany.
Rahimi
G
G
Hescheler
J
J
Wartenberg
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005318:Fetal Heart / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014812:Vitamin K / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D006861:Hydrogen Peroxide; D009025:Morpholines; D019255:NADPH Oxidases; D016877:Oxidants; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017382:Reactive Oxygen Species; D014812:Vitamin K; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one