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Critical role of phospholipase Cγ1 in the generation of H 2O2-evoked [Ca2+]i oscillations in cultured rat cortical astrocytes

Title
Critical role of phospholipase Cγ1 in the generation of H 2O2-evoked [Ca2+]i oscillations in cultured rat cortical astrocytes
Authors
Jeong H.H.Seok J.M.Hae M.B.Min S.K.Jo H.Yun S.B.Lee S.-I.Bootman M.D.Roderick H.L.Dong M.S.Jeong T.S.
Ewha Authors
배윤수
SCOPUS Author ID
배윤수scopus
Issue Date
2006
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 281, no. 19, pp. 13057 - 13067
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Reactive oxygen species, such as the superoxide anion, H2O 2, and the hydroxyl radical, have been considered as cytotoxic by-products of cellular metabolism. However, recent studies have provided evidence that H2O2 serves as a signaling molecule modulating various physiological functions. Here we investigated the effect of H2O2 on the regulation of intracellular Ca2+ signaling in rat cortical astrocytes. H2O2 triggered the generation of oscillations of intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner over the range 10-100 μM. The H2O2-induced [Ca 2+]i oscillations persisted in the absence of extracellular Ca2+ and were prevented by depletion of intracellular Ca2+ stores with thapsigargin. The H2O2-induced [Ca2+]i oscillations were not inhibited by pretreatment with ryanodine but were prevented by 2-aminoethoxydiphenyl borate and caffeine, known antagonists of inositol 1,4,5-trisphosphate receptors. H2O 2 activated phospholipase C (PLC) γ1 in a dose-dependent manner, and U73122, an inhibitor of PLC, completely abolished the H 2O2-induced [Ca2+]i oscillations. In addition, RNA interference against PLCγ1 and the expression of the inositol 1,4,5-trisphosphate-sequestering "sponge" prevented the generation of [Ca2+]i oscillations. H2O 2-induced [Ca2+]i oscillations and PLCγ1 phosphorylation were inhibited by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Finally, epidermal growth factor induced H 2O2 production, PLCγ1 activation, and [Ca 2+]i increases, which were attenuated by N-acetylcysteine and diphenyleneiodonium and by the overexpression of peroxiredoxin type II. Therefore, we conclude that low concentrations of exogenously applied H 2O2 generate [Ca2+]i oscillations by activating PLCγ1 through sulfhydryl oxidation-dependent mechanisms. Furthermore, we show that this mechanism underlies the modulatory effect of endogenously produced H2O2 on epidermal growth factor-induced Ca2+ signaling in rat cortical astrocytes. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M601726200
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자연과학대학 > 생명과학전공 > Journal papers
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