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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
- 배윤수
- Issue Date
- 2006
- Journal Title
- Journal of Biological Chemistry
- ISSN
- 0021-9258
- Citation
- Journal of Biological Chemistry vol. 281, no. 19, pp. 13057 - 13067
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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