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Journal of Gastroenterology
Published in: Journal of Gastroenterology 10/2011

01-10-2011 | Original Article—Alimentary Tract

Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells

Authors: Hirofumi Matsui, Yumiko Nagano, Osamu Shimokawa, Tsuyoshi Kaneko, Kanho Rai, Jumpei Udo, Aki Hirayama, Yukio Nakamura, Hiroko P. Indo, Hideyuki J. Majima, Ichinosuke Hyodo

Published in: Journal of Gastroenterology | Issue 10/2011

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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.
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Metadata
Title
Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells
Authors
Hirofumi Matsui
Yumiko Nagano
Osamu Shimokawa
Tsuyoshi Kaneko
Kanho Rai
Jumpei Udo
Aki Hirayama
Yukio Nakamura
Hiroko P. Indo
Hideyuki J. Majima
Ichinosuke Hyodo
Publication date
01-10-2011
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 10/2011
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0434-6

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