RRC ID 72969
Author Matsui H, Nagano Y, Shimokawa O, Kaneko T, Rai K, Udo J, Hirayama A, Nakamura Y, Indo HP, Majima HJ, Hyodo I.
Title Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells.
Journal J Gastroenterol
Abstract BACKGROUND:Gastric hydrochloric acid (HCl) has been regarded as an inciting factor in gastric mucosal injuries and has been reported to induce lipid peroxidation in vitro. However, because HCl is not an oxidant per se, the exact mechanism by which the acid induces lipid peroxidation is unknown. We hypothesized that gastric acid may disrupt mitochondrial transmembrane potential and induce the production of superoxide in mitochondria, which subsequently may induce lipid peroxidation and apoptosis in gastric mucosal cells.
METHODS:Firstly we treated gastric epithelial RGM1 cells with solutions containing various concentrations of HCl (i.e., of varying pH), and examined cellular injury, lipid peroxidation, and apoptosis with specific fluorescent dyes. Secondly, we performed electron paramagnetic resonance (EPR) spectroscopy of isolated, acid-exposed mitochondria from the cells, using a spin-trapping reagent for superoxide, 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO). Finally, we established novel RGM1 cells that overexpressed manganese superoxide dismutase (MnSOD), which removes superoxide from mitochondria, and examined the effect of acid treatment on cellular membrane lipid peroxidation.
RESULTS:The results indicated that the exposure to acid indeed induced cellular injury, cellular lipid peroxidation, apoptosis, and the demonstration of the exact superoxide spectra on EPR spectroscopy in gastric epithelial cells, and that overexpression of MnSOD decreased superoxide production and prevented cellular lipid peroxidation.
CONCLUSION:These results suggested that gastric acid, like nonsteroidal anti-inflammatory drugs (NSAIDs), induces mitochondrial superoxide production, which induces gastric cellular injury by triggering cellular lipid peroxidation and apoptosis.
Volume 46(10)
Pages 1167-76
Published 2011-10-1
DOI 10.1007/s00535-011-0434-6
PMID 21789481
MeSH Animals Apoptosis Cell Line Electron Spin Resonance Spectroscopy Epithelial Cells / metabolism* Gastric Acid / physiology* Gastric Mucosa / metabolism Gastric Mucosa / pathology* Hydrochloric Acid / administration & dosage Hydrochloric Acid / toxicity Hydrogen-Ion Concentration Lipid Peroxidation / physiology Membrane Potential, Mitochondrial / physiology Mitochondria / metabolism* Rats Superoxide Dismutase / metabolism Superoxides / metabolism
IF 6.132
Human and Animal Cells RGM1(RCB0876)