Phosphatidic acid-induced elevation of intracellular Ca2+ is mediated by RhoA and H2O2 in rat-2 fibroblasts

Zee Won Lee, Soo Mi Kweon, Byung Chul Kim, Sun Hee Leem, Incheol Shin, Jae-Hong Kim, Kwon Soo Ha

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Abstract

We have investigated possible roles of RhoA and H2O2 in the elevation of intracellular Ca2+ ([Ca2+](i)) by phosphatidic acid (PA) in Rat-2 fibroblasts. PA induced a transient elevation of [Ca2+](i) in the presence or absence of EGTA. Lysophosphatidic acid (LPA) also increased [Ca2+](i), but the sustained Ca2+ response was inhibited by EGTA. LPA stimulated the production of inositol phosphates, but PA did not. In the presence of EGTA, preincubation with LPA completely blocked the subsequent elevation of [Ca2+](i) by PA, but not vice versa. PA stimulated the translocation of RhoA to the particulate fraction as did LPA. Scrape loading of C3 transferase inhibited the transient Ca2+ response to PA, but not to LPA, suggesting an essential role of RhoA in the elevation of [Ca2+](i) by PA. H2O2 also induced a transient increase of [Ca2+](i) as did PA. H2O2 scavengers, catalase and N-acetyl-L-cysteine, completely blocked the rise of [Ca2+](i) stimulated by PA, but not by LPA. Furthermore, preincubation with PA blocked the subsequent Ca2+ response to H2O2, and the incubation with H2O2 also blocked the PA-induced rise of [Ca2+](i). Thus, it was suggested that PA stimulated Ca2+ release from PA-sensitive, but not inositol 1,4,5- trisphosphate-sensitive, Ca2+ stores by the activation of RhoA and intracellular H2O2.

Original languageEnglish
Pages (from-to)12710-12715
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number21
DOIs
Publication statusPublished - 1998 May 22
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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