Abstract
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.
MeSH terms
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Androstadienes / pharmacology
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Animals
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Cell Differentiation / drug effects
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Cell Line
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Chromones / pharmacology
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Enzyme Inhibitors / pharmacology
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Fetal Heart / cytology
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Fetal Heart / drug effects
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Fetal Heart / metabolism
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Hydrogen Peroxide / pharmacology
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Mice
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Morpholines / pharmacology
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Myocardium / cytology*
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Myocardium / metabolism*
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NADPH Oxidases / metabolism
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Oxidants / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Reactive Oxygen Species / metabolism*
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Signal Transduction
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Stem Cells / cytology
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Stem Cells / drug effects
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Stem Cells / metabolism
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Vitamin K / pharmacology
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Wortmannin
Substances
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Androstadienes
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Chromones
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Enzyme Inhibitors
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Morpholines
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Oxidants
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Phosphoinositide-3 Kinase Inhibitors
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Reactive Oxygen Species
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Vitamin K
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Hydrogen Peroxide
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NADPH Oxidases
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Wortmannin