Experimental researches on the role of phosphoinositide-specific phospholipase C in 4-hydroxynonenal induced exocytosis

✍ Scribed by Marina Maggiora; Maria Armida Rossi

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 89 KB
• Volume: 21
• Category: Article
• ISSN: 0263-6484
• DOI: 10.1002/cbf.1013

✦ Synopsis

Abstract

The action of 4‐hydroxynonenal (HNE), a chemotactic aldehyde produced by lipid peroxidation, was analysed on exocytosis in parallel with its effects on phosphoinositide‐specific phospholipase C (PLC) both in undifferentiated HL‐60 cells and in cells induced to differentiate toward the granulocytic cell line by 1.25% DMSO. Exocytosis was evaluated by the secretion of β‐glucuronidase from cells incubated at 37°C for 10 min in the presence of various aldehyde concentrations. HNE action was more pronounced in DMSO‐differentiated cells, where concentrations between 10^−8^ and 10^−6^ m were able both to trigger exocytosis and to strongly activate PLC; in both processes maximal stimulation was given by 10^−7^ m. HNE‐induced exocytosis was completely prevented by pertussis toxin and by the PLC inhibitor U73122. The comparison between HNE and formyl‐methionyl‐leucyl‐phenylalanine (fMLP), used as a positive control, showed that the tripeptide produced an higher stimulation of exocytosis than the aldehyde; by contrast HNE induced a stronger increase of PLC activity. Wortmannin, an inhibitor of phosphatidylinositol‐3‐kinase (PI3K), strongly inhibited the exocytosis induced by fMLP, while it failed to induce a statistically significant inhibition of HNE action. We conclude that both compounds trigger exocytosis through a Ptx‐sensitive G protein; the present data support the hypothesis that the lower ability of the aldehyde to trigger exocytosis as compared to fMLP might depend upon a low ability to activate PI3K, while PLC activation appears to play a key role in HNE‐induced exocytosis. Copyright © 2003 John Wiley & Sons, Ltd.