Zhangping Peng1, William J Arendshorst. 1. Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545, USA.
Abstract
BACKGROUND: We evaluated the effect of hydrogen peroxide (H2O2) on viability of vascular smooth muscle cells (VSMCs) of renal resistance arterioles and determined whether responses are modulated by activation of PLCgamma1. METHODS: Phospholipase C (PLC)-isozyme protein levels and activity were measured using Western blot analysis and enzymatic production of phosphoinositol 1,4,5-trisphosphate (IP3), respectively. Stimulation of PLCgamma1 was assessed by immunoblots of tyrosine phosphorylation. RESULTS: Cytotoxicity of H2O2 exposure was concentration-dependent (30% death with 250 microM; 87% with 500 microM at 8 h) and time-dependent (7% at 1 h; 30% at 8 h with 250 microM H2O2. Catalase abolished such relations. H2O2 increased PLCgamma1 expression more than that of PLCdelta1 and almost doubled total PLC enzymatic activity between 2 and 8 h, changes prevented by catalase. The PLC inhibitor U73112 (3 microM) enhanced the cytotoxic concentration and time effects of H2O2. In acute studies, H2O2 rapidly caused tyrosine phosphorylation of PLCgamma1. CONCLUSION: H2O2 increased PLCgamma1 expression and almost doubled total PLC activity, changes abolished by catalase. We conclude that H2O2 is cytotoxic to cultured VSMCs of renal preglomerular arterioles, a process that is attenuated by compensatory increases in PLCgamma1 protein level, tyrosine phosphorylation of PLCgamma1 and PLC enzymatic activity to generate IP3. (c) 2007 S. Karger AG, Basel
BACKGROUND: We evaluated the effect of hydrogen peroxide (H2O2) on viability of vascular smooth muscle cells (VSMCs) of renal resistance arterioles and determined whether responses are modulated by activation of PLCgamma1. METHODS: Phospholipase C (PLC)-isozyme protein levels and activity were measured using Western blot analysis and enzymatic production of phosphoinositol 1,4,5-trisphosphate (IP3), respectively. Stimulation of PLCgamma1 was assessed by immunoblots of tyrosine phosphorylation. RESULTS: Cytotoxicity of H2O2 exposure was concentration-dependent (30% death with 250 microM; 87% with 500 microM at 8 h) and time-dependent (7% at 1 h; 30% at 8 h with 250 microM H2O2. Catalase abolished such relations. H2O2 increased PLCgamma1 expression more than that of PLCdelta1 and almost doubled total PLC enzymatic activity between 2 and 8 h, changes prevented by catalase. The PLC inhibitor U73112 (3 microM) enhanced the cytotoxic concentration and time effects of H2O2. In acute studies, H2O2 rapidly caused tyrosine phosphorylation of PLCgamma1. CONCLUSION:H2O2 increased PLCgamma1 expression and almost doubled total PLC activity, changes abolished by catalase. We conclude that H2O2 is cytotoxic to cultured VSMCs of renal preglomerular arterioles, a process that is attenuated by compensatory increases in PLCgamma1 protein level, tyrosine phosphorylation of PLCgamma1 and PLC enzymatic activity to generate IP3. (c) 2007 S. Karger AG, Basel
Authors: M R Brown; F J Miller; W G Li; A N Ellingson; J D Mozena; P Chatterjee; J F Engelhardt; R M Zwacka; L W Oberley; X Fang; A A Spector; N L Weintraub Journal: Circ Res Date: 1999-09-17 Impact factor: 17.367
Authors: Norbert Weissmann; Akylbek Sydykov; Hermann Kalwa; Ursula Storch; Beate Fuchs; Michael Mederos y Schnitzler; Ralf P Brandes; Friedrich Grimminger; Marcel Meissner; Marc Freichel; Stefan Offermanns; Florian Veit; Oleg Pak; Karl-Heinz Krause; Ralph T Schermuly; Alison C Brewer; Harald H H W Schmidt; Werner Seeger; Ajay M Shah; Thomas Gudermann; Hossein A Ghofrani; Alexander Dietrich Journal: Nat Commun Date: 2012-01-31 Impact factor: 14.919