title: Phosphatidic acid-induced elevation of intracellular Ca2+ is mediated by RhoA and H2O2 in Rat-2 fibroblasts.
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.
authors.affiliation: Biomolecule Research Group, Korea Basic Science Institute, Taejon 305-333, Korea.
authors.forename: Z W
authors.initials: ZW
authors.lastname: Lee
authors.forename: S M
authors.initials: SM
authors.lastname: Kweon
authors.forename: B C
authors.initials: BC
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Leem
authors.forename: I
authors.initials: I
authors.lastname: Shin
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: K S
authors.initials: KS
authors.lastname: Ha
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000494:pharmacology*; D051381:Rats; D020742:rhoA GTP-Binding Protein
chemical_list: D010712:Phosphatidic Acids; D006861:Hydrogen Peroxide; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D002118:Calcium