Methylmercury stimulates arachidonic acid release and cytosolic phospholipase A₂ expression in primary neuronal cultures

Cytosolic phospholipase A₂ (cPLA₂) plays an important role in the stimulus-dependent hydrolysis of sn-2 ester bond from membrane phospholipids, releasing arachidonic acid (AA), which along with its metabolites is involved in a number of regulatory functions. The present study examined the effect of methylmercury (MeHg; 0, 2.5, 5.0μM) on cPLA ₂ activation in primary hippocampal neurons by assessing the release of ³H-AA. A significant increase in AA release was observed in cultures treated with 5μM MeHg (10, 30, 60 and 120min). This effect was due to neuronal cPLA₂ activation, since it was completely abolished by arachidonyl trifluoromethyl ketone (AACOCF₃), a specific inhibitor of cPLA₂. Additional studies confirmed, by means of western blot analysis, that MeHg (5.0 and 10μM; 16h) potently increases neuronal cPLA ₂ protein expression. These results suggest that cPLA ₂-stimulated hydrolysis and release of AA are potential mediators of MeHg-induced neurotoxicity.