Curcumin modulates PKCα activity by a membrane-dependent effect.

Curcumin modulates the activity of protein kinase Cα (PKCα) when assayed in the presence of vesicles including phosphatidylcholine, phosphatidylserine and diacylglycerol. Increasing concentrations of curcumin progressively increased PKCα activity at concentrations lower than 20μM, but at higher concentrations of curcumin the activity decreased although, at concentrations of curcumin of up to 100μM the activity was always higher than the basal one (in the absence of curcumin). The maximum activity was reached at 3μM curcumin, at 20 and 30mol% of phosphatidylserine, 10μM Ca(2+) and 2mol% diacylglycerol. The same type of modulation was observed when changing the concentration of phosphatidylserine, diacylglycerol and Ca(2+). No effect of curcumin was found when the activity was assayed in the presence of Triton X-100 mixed micelles which included phosphatidylserine and diacylglycerol, indicating that the effect of curcumin was membrane-dependent. The pattern of binding of PKCα to membrane vesicles as a function of curcumin concentration closely correlated with the pattern of activating effect. It was concluded that the effect of curcumin on PKCα activity was related to its effect on the membrane, which may modulate the binding of the enzyme to the membrane.