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Hydrogen Peroxide Enhances Signal‐Responsive Arachidonic Acid Release from Neurons: Role of Mitogen‐Activated Protein Kinase
Author(s) -
Samanta Sujon,
Perkinton Michael S.,
Morgan Michael,
Williams Robert J.
Publication year - 1998
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.1471-4159.1998.70052082.x
Subject(s) - hydrogen peroxide , arachidonic acid , protein kinase a , chemistry , mitogen activated protein kinase , mitogen activated protein kinase kinase , microbiology and biotechnology , ask1 , kinase , biochemistry , biology , enzyme
Hydrogen peroxide (H 2 O 2 ) is a potent stimulator of signal‐responsive phospholipase A 2 (PLA 2 ) in vascular smooth muscle and cultured endothelial cells. We investigated whether H 2 O 2 plays a similar regulatory role in neurons. H 2 O 2 did not stimulate a release of arachidonic acid from cultured neurons when applied alone but strongly enhanced the liberation of arachidonic acid evoked by maximally effective concentrations of either glutamate, the glutamate receptor agonist N ‐methyl‐ d ‐aspartate (NMDA), the muscarinic receptor agonist carbachol, the Na + ‐channel opener veratridine, or the Ca 2+ ‐ionophore ionomycin. The potentiating effects of H 2 O 2 were strongly inhibited in the presence of the PLA 2 inhibitor mepacrine, suggesting that the site of action was within the signal responsive arachidonic acid cascade. The enhancing effect of H 2 O 2 was not reversed by protein kinase C inhibitors (chelerythrine chloride or GF 109203X) nor was it mimicked by phorbol ester treatment. H 2 O 2 alone strongly enhanced the levels of immunodetectable activated mitogen‐activated protein kinase (activated MAP kinases ERK1 and ERK2) in a Ca 2+ ‐dependent manner and this effect was additive with increases in the levels of activated MAP kinase evoked by glutamate. The enhanced release of arachidonic acid, however, was not clearly reversed by the MAP kinase kinase (MEK) inhibitor PD 98059, although this treatment effectively abolished H 2 O 2 activation of MAP kinase. Thus, MAP kinase activation and Ca 2+ ‐dependent arachidonic acid release are regulated by oxidative stress in cultured striatal neurons.