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

Abstract

The effects of some 4-hydroxyalkenals, carbonylic products of lipid peroxidation, on hepatic phosphatidylinositol-4,5-bisphosphate (PIP 2)-phospholipase C (PL-C) activity were investigated. The enzymatic activity was assayed in vitro by measuring the hydrolysis of [ 3H]PIP 2 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 PIP 2 breakdown at concentrations between 10 −12 and 10 −6M, 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 PIP 2 breakdown at doses which can be actually reached in tissues, the effects shown in vitro are likely to occur in vivo.