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Critical Role of Phospholipase Cγ1 in the Generation of H2O2-evoked [Ca2+]i Oscillations in Cultured Rat Cortical Astrocytes

 Jeong Hee Hong  ;  Seok Jun Moon  ;  Hae Mi Byun  ;  Min Seuk Kim  ;  Hae Jo  ;  Yun Soo Bae  ;  Syng-Ill Lee  ;  Martin D. Bootman  ;  H. Llewelyn Roderick  ;  Dong Min Shin  ;  Jeong Taeg Seo 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.281(19) : 13057-13067, 2006 
Journal Title
Issue Date
Animals ; Astrocytes/drug effects* ; Astrocytes/metabolism* ; Calcium/metabolism* ; Calcium Signaling/drug effects* ; Cells, Cultured ; Cerebral Cortex/cytology* ; Dose-Response Relationship, Drug ; Enzyme Activation ; Epidermal Growth Factor ; Estrenes ; Hydrogen Peroxide/pharmacology* ; Inositol 1,4,5-Trisphosphate/metabolism ; Phospholipase C gamma/antagonists & inhibitors ; Phospholipase C gamma/metabolism* ; Pyrrolidinones ; Rats ; Rats, Wistar ; Thapsigargin
Reactive oxygen species, such as the superoxide anion, H2O2, 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 microM. The H2O2-induced [Ca2+]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. H2O2 activated phospholipase C (PLC) gamma1 in a dose-dependent manner, and U73122, an inhibitor of PLC, completely abolished the H2O2-induced [Ca2+]i oscillations. In addition, RNA interference against PLCgamma1 and the expression of the inositol 1,4,5-trisphosphate-sequestering "sponge" prevented the generation of [Ca2+]i oscillations. H2O2-induced [Ca2+]i oscillations and PLC1 phosphorylation were inhibited by pretreatment with dithiothreitol, a sulfhydryl-reducing agent. Finally, epidermal growth factor induced H2O2 production, PLCgamma1 activation, and [Ca2+]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 H2O2 generate [Ca2+]i oscillations by activating PLCgamma1 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.
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Moon, Seok Jun(문석준) ORCID logo https://orcid.org/0000-0001-7282-2888
Seo, Jeong Taeg(서정택) ORCID logo https://orcid.org/0000-0003-2697-0251
Shin, Dong Min(신동민) ORCID logo https://orcid.org/0000-0001-6042-0435
Lee, Syng Ill(이승일)
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