EFFECT OF 4-HYDROXY-2,3-TRANS-NONENAL AND RELATED ALDEHYDES ON PHOSPHOLIPASE-C ACTIVITY OF RAT NEUTROPHILS

Our work has evaluated the effects of certain lipid peroxidation produ cts, i.e. 4-hydroxy-2,3-trans-nonenal (HNE), 4-hydroxy-2,3-trans-octen al (HOE), 2-trans-nonenal and nonanal, on phosphoinositide-specific ph ospholipase C (PL-C). The enzymatic activity has been determined in vi tro by measuring the hydrolysis oi labelled phosphatidylinositol-4,5-b isphosphate added to plasma membranes isolated from rat neutrophils. C oncentrations of HNE between 10(-8) and 10(-6) M, and concentrations o f HOE ranging from 10(-11) to 10(-8) M, were able to activate PL-C. Ne ither 2-trans-nonenal nor nonanal induced any change of PL-C activity. HNE, HOE and 2-nonenal, but not nonanal, have been shown to possess c hemotactic properties towards rat neutrophils. The good correlation be tween the concentrations oi HNE and HOE active on PL-C and those able to stimulate cell migration suggests that their chemotactic activity m ight be mediated by the activation oi PL-C, as in the case oi most che moattractants. On the contrary, this mechanism oi action cannot be app lied to 2-nonenal, an aldehyde much more hydrophobic than HNE or HOE; its chemotactic activity might be the consequence oi some perturbation oi the lipidic environment oi the cell membrane where it dissolves ea sily.