Experimental studies on the mechanism of action of 4-hydroxy-2,3-trans-nonenal, a lipid peroxidation product displaying chemotactic activity toward rat neutrophils.
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.
Rossi
M A
MA
Department of Experimental Medicine and Oncology, University of Turin, Torino, Italy.
Curzio
M
M
Di Mauro
C
C
Fidale
F
F
Garramone
A
A
Esterbauer
H
H
Torrielli
M
M
Dianzani
M U
MU
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*
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