Effects of oxidative stress on phospholipid signaling in rat cultured astrocytes and brain slices

Joan Marc Servitja, Roser Masgrau, Raúl Pardo, Elisabet Sarri, Fernando Picatoste

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

Abstract

Although reactive oxygen species (ROS) are conventionally viewed as toxic by-products of cellular metabolism, a growing body of evidence suggests that they may act as signaling molecules. We have studied the effects of hydrogen peroxide (H2O2)-induced oxidative stress on phospholipid signaling in cultured rat cortical astrocytes. H2O2 stimulated the formation of phosphatidic acid and the accumulation of phosphatidylbutanol, a product of the phospholipase D (PLD)-catalyzed transphosphatidylation reaction. The effect of exogenous H2O2 on the PLD response was mimicked by menadione- induced production of endogenous H2O2. Oxidative stress also elicited inositol phosphate accumulation resulting from phosphoinositide phospholipase C (PLC) activation. The PLD response to H2O2 was totally suppressed by chelation of both extracellular and cytosolic Ca2+ with EGTA and BAPTA/AM, respectively. Furthermore, H2O2-induced PLD stimulation was completely abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide and chelerythrine and by PKC down-regulation. Activation of PLD by H2O2 was also inhibited by the protein-tyrosine kinase inhibitor genistein. Finally, H2O2 also stimulated both PLC and PLD in rat brain cortical slices. These results show for the first time that oxidative stress elicits phospholipid breakdown by both PLC and PLD in rat cultured astrocytes and brain slices.
Original languageEnglish
Pages (from-to)788-794
JournalJournal of Neurochemistry
Volume75
DOIs
Publication statusPublished - 7 Aug 2000

Keywords

  • Astrocytes
  • Brain slices
  • Hydrogen peroxide
  • Oxidative stress
  • Phospholipase C
  • Phospholipase D

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