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.
Rossi
M A
MA
Department of Experimental Medicine and Oncology, University of Turin, Italy.
Fidale
F
F
Garramone
A
A
Esterbauer
H
H
Dianzani
M U
MU
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D005978:Glutathione / Q000494:pharmacology; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology*; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D010738:Type C Phospholipases / Q000378:metabolism*
D000447:Aldehydes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; C045934:4-hydroxy-2-hexenal; C046538:4-hydroxy-2-octenal; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D005978:Glutathione; C027576:4-hydroxy-2-nonenal