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

Gouri Shanker, Robert E. Hampson, Michael Aschner

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19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
JournalNeuroToxicology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 1 2004
Externally publishedYes

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Keywords

  • Arachidonic acid
  • Cytosolic phospholipase A
  • Hippocampal neurons
  • In vitro
  • Methylmercury
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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