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 20 μM, but at higher concentrations of curcumin the activity decreased although, at concentrations of curcumin of up to 100 μM the activity was always higher than the basal one (in the absence of curcumin). The maximum activity was reached at 3 μM curcumin, at 20 and 30 mol% of phosphatidylserine, 10 μM Ca2+ and 2 mol% diacylglycerol. The same type of modulation was observed when changing the concentration of phosphatidylserine, diacylglycerol and Ca2+. 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.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (158 K)Download as PowerPoint slideHighlights► We assay the effect of curcumin on PKCα activated by different phospholipid composition and Ca2+ concentrations. ► Curcumin produced a biphasic effect on PKCα activity with activation at low concentrations. ► The activation induced by curcumin disappeared at high concentrations. ► Curcumin did not activated PKCα in the presence of mixed Triton X-100 vesicles. ► Curcumin modulates the binding of PKCα to phospholipid vesicles with a similar pattern to that of activity.