Action of 2-nonenal and 4-hydroxynonenal on phosphoinositide-specific phosopholipase C in undifferentiated and DMSO-differentiated HL-60 cells.
The promyelocytic cell line HL-60 has been used as an in vitro model to study the mechanism of action of two chemotactic aldehydes, 2-nonenal and 4-hydroxynonenal. Increasing aldehyde concentrations have been added to undifferentiated and DMSO-differentiated cells incubated at 37 degrees C and their effect on phosphoinositide-specific phospholipase C has been analysed by using a specific inositol-1,4,5-tris-phosphate assay system. Concentrations of 2-nonenal between 10(-9) and 10(-7) M significantly increased the enzymatic-activity in DMSO-differentiated HL-60 cells, while 10(-9) and 10(-8) M concentrations were active in the undifferentiated cells. 4-Hydroxynonenal was able to activate phospholipase C both in undifferentiated and DMSO-differentiated cells at concentrations ranging from 10(-8) to 10(-6) M. The concentrations of both compounds active on phospholipase C displayed a good correspondence with those which had been reported to be chemotactic towards rat neutrophils. In the case of 4-hydroxynonenal, the present results confirm its ability to activate phospholipase C, which we had previously shown in isolated neutrophil plasma membranes. The comparison of the effects of 2-nonenal and 4-hydroxynonenal on chemotaxis and phospholipase C activation suggests a common mechanism of action for both aldehydes, for which the presence of the double bond seems to be required.
Rossi
M A
MA
Department of Experimental Medicine and Oncology, Section of General Pathology, University of Turin, Corso Raffaello 30, 10125 Torino, Italy.
Dianzani
M U
MU
D000135:Acid Phosphatase / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D002633:Chemotaxis / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D016166:Free Radical Scavengers / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008024:Ligands; D015227:Lipid Peroxidation / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D016166:Free Radical Scavengers; D008024:Ligands; C013166:2-nonenal; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015544:Inositol 1,4,5-Trisphosphate; D000135:Acid Phosphatase; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C027576:4-hydroxy-2-nonenal; D004121:Dimethyl Sulfoxide