caa a22 4500 445888482 CHVBK 20180317145607.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s00535-011-0434-6 doi (NATIONALLICENCE)springer-10.1007/s00535-011-0434-6 Gastric acid induces mitochondrial superoxide production and lipid peroxidation in gastric epithelial cells [Elektronische Daten] [Hirofumi Matsui, Yumiko Nagano, Osamu Shimokawa, Tsuyoshi Kaneko, Kanho Rai, Jumpei Udo, Aki Hirayama, Yukio Nakamura, Hiroko Indo, Hideyuki Majima, Ichinosuke Hyodo] 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. Springer, 2011 Gastric acid nationallicence Lipid peroxidation nationallicence Superoxide (O 2 ·− ) nationallicence Mitochondria nationallicence Manganese superoxide dismutase (MnSOD) nationallicence Matsui Hirofumi The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Nagano Yumiko The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Shimokawa Osamu The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Kaneko Tsuyoshi The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Rai Kanho The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Udo Jumpei The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Hirayama Aki The Center of Integrative Medicine, Tsukuba University of Technology, 4-12-7 Kasuga, 305-8575, Tsukuba, Ibaraki, Japan aut Nakamura Yukio Cell Engineering Division, RIKEN BioResource Center, 3-1-1 Koyadai, 305-0074, Tsukuba, Ibaraki, Japan aut Indo Hiroko The Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8544, Kagoshima, Japan aut Majima Hideyuki The Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8544, Kagoshima, Japan aut Hyodo Ichinosuke The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1167-1176 0944-1174 46:10<1167 2011 46 535 https://doi.org/10.1007/s00535-011-0434-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00535-011-0434-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Matsui Hirofumi The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Nagano Yumiko The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Shimokawa Osamu The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Kaneko Tsuyoshi The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Rai Kanho The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Udo Jumpei The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Hirayama Aki The Center of Integrative Medicine, Tsukuba University of Technology, 4-12-7 Kasuga, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Nakamura Yukio Cell Engineering Division, RIKEN BioResource Center, 3-1-1 Koyadai, 305-0074, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Indo Hiroko The Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Majima Hideyuki The Department of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 890-8544, Kagoshima, Japan aut NATIONALLICENCE 700 1- Hyodo Ichinosuke The Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, 305-8575, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 773 0- Journal of Gastroenterology Springer Japan 46/10(2011-10-01), 1167-1176 0944-1174 46:10<1167 2011 46 535 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer