title: Experimental studies on the mechanism of action of 4-hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils.
abstract: The effects of 4-hydroxy-2,3-trans-nonenal (HNE) and nonanal on the activity of phosphoinositide-specific phospholipase C of rat neutrophils have been studied in parallel with their action on neutrophil oriented migration. Concentrations of HNE ranging from 10(-7) to 10(-5) M significantly stimulated the oriented migration of rat polymorphonuclear leukocytes. HNE stimulated both the basal and GTP gamma S-induced phospholipase C activity when used at concentrations between 10(-8) and 10(-6) M. Nonanal was devoid both of chemotactic activity and of any action on phospholipase C activity. The effect of GTP gamma S on the stimulation of phospholipase C induced by HNE was higher when the lowest dose of the aldehyde was used; the finding of an additive effect between 10(-8) M HNE and 2 x 10(-5) M GTP gamma S suggests that the two compounds may share a final common pathway of action. These results suggest that the chemotactic activity of HNE might be mediated, like that of other more well-known chemoattractants, by the stimulation of phosphoinositide-specific phospholipase C.
authors.affiliation: Department of Experimental Medicine and Oncology, University of Turin, Torino, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Curzio
authors.forename: C
authors.initials: C
authors.lastname: Di Mauro
authors.forename: F
authors.initials: F
authors.lastname: Fidale
authors.forename: A
authors.initials: A
authors.lastname: Garramone
authors.forename: H
authors.initials: H
authors.lastname: Esterbauer
authors.forename: M
authors.initials: M
authors.lastname: Torrielli
authors.forename: M U
authors.initials: MU
authors.lastname: Dianzani
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D004790:Enzyme Induction; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D015227:Lipid Peroxidation; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; C008664:nonanal; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010738:Type C Phospholipases; C027576:4-hydroxy-2-nonenal