Effect of 4-hydroxylalkenals on hepatic phosphatidylinositol-4,5-bisphosphate-phospholipase C.

The effects of some 4-hydroxyalkenals, carbonylic products of lipid peroxidation, on hepatic phosphatidylinositol-4,5-bisphosphate (PIP2)-phospholipase C (PL-C) activity were investigated. The enzymatic activity was assayed in vitro by measuring the hydrolysis of [3H]PIP2 added as exogenous substrate to liver membranes. 4-Hydroxyhexenal (HEE), 4-hydroxyoctenal (HOE) and 4-hydroxynonenal (HNE) were able to stimulate both the basal and the GTPgammaS induced PL-C activity, whereas 4-hydroxyundecenal was inactive. HOE was the most active compound, being able to accelerate PIP2 breakdown at concentrations between 10(-12) and 10(-6) M, while in the case of HEE the effective doses ranged from 10(-11) to 10(-7) M and from 10(-9) to 10(-6) M in the case of HNE. 4-Hydroxynonenal was able to increase also bombesin stimulated PL-C activity. As these aldehydes accelerated PIP2 breakdown at doses which can be actually reached in tissues, the effects shown in vitro are likely to occur in vivo.