Lipid products of phosphoinositide 3-kinase abrogate genistein-induced fusion inhibition in myoblasts.
Genistein (4',5,7-trihydroxyisoflavone) is a tyrosine kinase inhibitor. Although the agent has shown to inhibit myoblast differentiation, neither intracellular target(s) as a tyrosine kinase inhibitor nor action mechanism of the agent is well known. Here we studied the effect of genistein on the differentiation of myoblasts. Genistein strongly but reversibly blocked both myoblast fusion and synthesis of the muscle-specific proteins. The agent also reversibly reduced the phosphorylation level of focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, and its interaction with p85, the regulatory subunit of phosphoinositide 3-kinase (PI3-kinase). In addition, genistein indirectly inhibited PI3-kinase activity and blocked calcium influx which is required for myoblast fusion. However, both genistein-induced inhibition of cell fusion and calcium influx were abrogated by the lipid products of PI3-kinase. These results demonstrate that genistein can exert their effect on the signaling pathway from FAK to calcium influx via PI3-kinase in the differentiation of myoblasts.
Woo
Joo Hong
JH
Department of Biological Science, College of Natural Sciences, Ajou University, Suwon 443-749, Republic of Korea.
Kim
Jeong Heon
JH
Inhee
Mook-Jung
MJ
Kim
Hye Sun
HS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D008055:Lipids / Q000494:pharmacology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051381:Rats
D002118:Calcium; D004791:Enzyme Inhibitors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019833:Genistein; D008055:Lipids; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors