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Lipid products of phosphoinositide 3-kinase abrogate genistein-induced fusion inhibition in myoblasts

Cited 8 time in Web of Science Cited 8 time in Scopus
Authors
Woo, Joo Hong; Kim, Jeong Heon; Mook-Jung, Inhee; Kim, Hye Sun
Issue Date
2006
Publisher
Elsevier
Citation
Eur. J. Pharmacol. 529, 84-94
Keywords
1-Phosphatidylinositol 3-Kinase/*antagonists & inhibitors/metabolismAnimalsCalcium/metabolismCell Differentiation/*drug effectsCell FusionCells, CulturedEnzyme Inhibitors/*pharmacologyFocal Adhesion Protein-Tyrosine Kinases/metabolismGenistein/*pharmacologyLipids/*pharmacologyMyoblasts, Skeletal/cytology/*drug effectsPhosphorylationRats
Abstract
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.
ISSN
0014-2999 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16360147

http://hdl.handle.net/10371/24862
DOI
https://doi.org/10.1016/j.ejphar.2005.11.007
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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