Effects of Isoflavone Compounds on the Activation of Phospholipase C

概要

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The effect of isoflavone compounds, genistein and daidzein, on the breakdown of inositol phospholipids in 3T3 cells was studies. Genistein (100μg/ml) inhibited the sitmulation of the production of inositol phosphates by bombesin. The stimulated production of inositol phosphates by AlF^-_4 was also inhibited by genistein (IC_<50>=0.6μg/ml)and daidzein (IC<50>=2μg/ml). However, the catalytic activity of phospholipase-C (PLC) in 3T3 cell extracts was not inhibited by these isoflavones. These results suggest that the isoflavones inhibited the activation of PLC at the G-protein or downstream of the sequences in signal transduction.In permeabilized 3T3 cells, the inhibition of AlF^-_4 plus adenosine triphosphate (ATP)-dependent PLC was recovered by increasing ATP but not AlF^-_4. Genistein also inhibited the activity of adenosin 5'-[3-O-thiotriphosphate](ATP[S])-dependent PLC. The effect of genistein and other inhibitors of protein tryrosine kinases and phosphatases suggests that protein tyrosine phosphorylation is not involved in the activation of PLC in 3T3 cells and that AlF^-_4-and ATP[S]-mediated activation of PLC involves a different mechanism from the tyrosine kinase-mediated activtion of PLC.Daidzein and genistein seem to interrupt the ATP-dependent step of PLC activation by a putative G-protein.
公益社団法人日本薬学会の論文
1992-01-25