Role of reactive oxygen species and phosphatidylinositol 3‐kinase in cardiomyocyte differentiation of embryonic stem cells

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 H2O2 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.