No abstract

The effect on the phospholipase C gamma 1 activity of eleven prenylated flavonoids from Sophora flavescens was investigated. These flavonoids exhibited relatively strong inhibitory activity with IC50 values ranged from 7.5 x 10(-6) M to 35 x 10(-5) M with the exception of kushenol H (4) (IC50 value; > 5.3 x 10(-4) M). The presence of C3-OH resulted in a significant diminution of activity and the configuration of C3-OH is likely to be another factor influencing the activity. In addition, hydration of the C-4"'-C-5"' double bond of the lavandulyl side chain caused complete loss of activity. These data suggest that the presence and configuration of C3-OH are related to the inhibitory activity and the lavandulyl side chain is also important for high inhibitory activity against PLC gamma 1.

Herbimycin A, an inhibitor of protein tyrosine kinases, dose-dependently reduced PDGF-induced inositol phosphates (IPt) accumulation without effect on phosphatidylethanol (PEt) formation in PLC-gamma 1-overexpressing NIH 3T3 (NIH 3T3 gamma 1) cells. The compound also reduced tyrosine phosphorylations of some proteins including PLC-gamma 1 in response to PDGF. On the other hand, phorbol 12-myristate 13-acetate (PMA)-induced phospholipase D (PLD) activation was reduced by herbimycin A in the cells, indicating that the pathways for PLD activation by PDGF and PMA are different from each other. Also, these results suggest that PLC-gamma 1 activation is not always an upstream event for PLD activation and that tyrosine phosphorylation of one or more proteins not affected by herbimycin A should be indispensable for PLD activation in PDGF-stimulated NIH 3T3 gamma 1 cells.

SummaryIn tsRSV-infected NRK (tsNRK) cells, pp60 v-src reactivation by temperature-shift from a nonpermissive temperature, 39 ± C, to a permissive one, 32 ± C, induced the production of inositol phosphates (IPt) and phosphatidylethanol (PEt). This was accompanied by an increase in membrane-associated protein kinase C (PKC) activity in the absence of exogenous growth factors. However, with serum-stimulation, the amounts of IPt and PEt at 32 ± C were less than those at 39 ± C. Pretreatment with PKC inhibitors, Ro-31-8220 and staurosporine, enhanced the accumulation of IPt but not of PEt at 32 ± C. The tyrosine phosphorylation of phospholipase C°1 (PLC°1) was increased either by serum or by pp60 v-src reactivation. These results suggest that serum transduces its signal through PLC°1 mediation, and that pp60 v-src , possibly through the PKC mediation, negatively affects serum-induced PLC°1 activation. IUBMB Life, 48: 85± 89, 1999

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