Activation of phosphoinositide-specific phospholipase C of rat neutrophils by the chemotactic aldehydes 4-hydroxy-2,3-trans-nonenal and 4-hydroxy-2,3-trans-octenal.
A comparison has been made between the effects of 4-hydroxy-2,3-trans-nonenal (HNE) and 4-hydroxy-2,3-trans-octenal (HOE), two lipid peroxidation products, on the basal and GTPgammaS-stimulated activities of phosphoinositide-specific phospholipase C (PL-C) of rat polymorphonuclear leukocytes. PL-C activity was determined in vitro by measuring the hydrolysis of [3H] phosphatidylinositol-4,5-bis- phosphate (PtdIns-P2) added as exogenous substrate to neutrophil plasma membranes. PL-C was activated by concentrations of HNE ranging from 10(-8) to 10(-6) M both in the presence and in the absence of 2 x 10(-5) M GTPgammaS; HOE stimulated the enzymatic activity between 10(-11) and 10(-8) M; maximal stimulation was given by 10(-11) M HOE plus GTPgammaS. The aldehyde concentrations able to accelerate PtdIns-P2 breakdown displayed a good correspondence with those which have been reported to stimulate the oriented migration of rat neutrophils. Pretreatment of neutrophils with pertussis toxin prevented the stimulation of PL-C by 10(-11) M HOE and by HOE plus GTPgammaS. Our results suggest that the chemotactic action of HNE and HOE might depend on the activation of PL-C; furthermore a regulatory G protein appears to be involved in the acceleration of PtdIns-P2 turnover by HOE.
Department of Experimental Medicine, University of Turin, Italy.
M A
MA
Rossi
C
C
Di Mauro
H
H
Esterbauer
F
F
Fidale
M U
MU
Dianzani
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006160:Guanosine Triphosphate / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D037342:Pertussis Toxin; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D051381:Rats; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000447:Aldehydes; D010566:Virulence Factors, Bordetella; C046538:4-hydroxy-2-octenal; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C027576:4-hydroxy-2-nonenal