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Effects of Oxidative Stress on Phospholipid Signaling in Rat Cultured Astrocytes and Brain Slices
Author(s) -
Servitja JoanMarc,
Masgrau Roser,
Pardo Raúl,
Sarri Elisabet,
Picatoste Fernando
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750788.x
Subject(s) - phosphatidic acid , protein kinase c , phospholipase d , oxidative stress , chelerythrine , biochemistry , bisindolylmaleimide , phospholipase c , chemistry , microbiology and biotechnology , biology , signal transduction , phospholipid , membrane
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 (H 2 O 2 )‐induced oxidative stress on phospholipid signaling in cultured rat cortical astrocytes. H 2 O 2 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 H 2 O 2 on the PLD response was mimicked by menadione‐induced production of endogenous H 2 O 2 . Oxidative stress also elicited inositol phosphate accumulation resulting from phosphoinositide phospholipase C (PLC) activation. The PLD response to H 2 O 2 was totally suppressed by chelation of both extracellular and cytosolic Ca 2+ with EGTA and BAPTA/AM, respectively. Furthermore, H 2 O 2 ‐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 H 2 O 2 was also inhibited by the protein‐tyrosine kinase inhibitor genistein. Finally, H 2 O 2 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.