No abstract

Evidence is emerging that resveratrol (RV), a polyphenolic phytoaxelin present in dietary sources including red wine, may protect against atherosclerosis and cardiovascular disease by enhancing the integrity of the endothelium. In this study, the possibility that such beneficial effects of RV may arise from a modulation of protein kinase C (PKC)-mediated signaling was investigated by determining the effects of RV on the in vitro activities of PKC isozymes. It was found that the Ca(2+)-dependent activities of membrane-associated PKCalpha induced by either phorbol ester or diacylglycerol were potently inhibited by RV, each with an IC(50) of approximately 2 microM. The inhibitory effect of RV was also observed for conventional PKCbetaI, whereas the activities of novel PKC epsilon and atypical PKCzeta were each unaffected. The inhibition of PKCalpha activity was found to be competitive with respect to phorbol ester concentration but noncompetitive with respect to Ca(2+) and phosphatidylserine concentrations, suggesting that the RV may compete for phorbol ester-binding to the C1 domains. Supporting this, it was found that RV bound to a fusion peptide containing the C1A and C1B domains of PKCalpha. Similar to the effects of diacylglycerol and phorbol ester, the interaction of RV with the C1 domains induced the association of PKCalpha with membrane lipid vesicles, although this did not result in activation. Overall, the results suggest that the inhibitory effect of RV on PKC activity, and therefore on the associated signaling networks, may, in part, underlie the mechanism(s) by which this agent exerts its beneficial effects on endothelial and cardiovascular function. Furthermore, the effects of RV on these signaling networks are predicted to differ according to the cellular localization and the regulating PKC isozyme.

.[1] Insight into the mechanical and thermal structure of Mercury's early lithosphere has been obtained from forward modeling of the largest lobate scarp known on the planet. Our modeling indicates the structure overlies a thrust fault that extends deep into Mercury's lithosphere. The best-fitting fault parameters are a depth of faulting of 35 to 40 km, a fault dip of 30°to 35°, and a displacement of $2 km. The Discovery Rupes thrust fault probably cut the entire elastic and seismogenic lithosphere when it formed ($4.0 Gyr ago). On Earth, the maximum depth of faulting is thermally controlled. Assuming the limiting isotherm for Mercury's crust is $300°to 600°C and it occurred at a depth of $40 km, the corresponding heat flux at the time of faulting was $10 to 43 mW m À2. This is less than old terrestrial oceanic lithosphere but greater than the present heat flux on the Moon.