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Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells
Alpha-ketoglutarate, a key intermediate in the Krebs cycle, has been reported to benefit intestinal health. We tested whether alpha-ketoglutarate can protect intestinal cells against hydrogen peroxide induced damage and aimed to reveal the underlying mechanism. Intestinal porcine epithelial cell lin...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650381/ https://www.ncbi.nlm.nih.gov/pubmed/29088826 http://dx.doi.org/10.18632/oncotarget.20426 |
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author | Jiang, Qian Liu, Gang Wang, Xiuqi Hou, Yongqing Duan, Yehui Wu, Guoyao Yin, Yulong Yao, Kang |
author_facet | Jiang, Qian Liu, Gang Wang, Xiuqi Hou, Yongqing Duan, Yehui Wu, Guoyao Yin, Yulong Yao, Kang |
author_sort | Jiang, Qian |
collection | PubMed |
description | Alpha-ketoglutarate, a key intermediate in the Krebs cycle, has been reported to benefit intestinal health. We tested whether alpha-ketoglutarate can protect intestinal cells against hydrogen peroxide induced damage and aimed to reveal the underlying mechanism. Intestinal porcine epithelial cell line J2 were cultured in Dulbecco’s Modified Eagle Medium-High glucose with or without alpha-ketoglutarate and hydrogen peroxide. Cell viability, proliferation, mitochondrial respiration, mitochondrial membrane potential, antioxidant function, apoptosis and mitochondrial-dependent apoptotic pathways were determined. Our experiments demonstrated that, first, exposure to 100μM hydrogen peroxide decreased cell viability, DNA synthesis, mitochondrial respiration and antioxidant function, and increased apoptosis. Second, 2mM alpha-ketoglutarate addition attenuated hydrogen peroxide-induced cell cycle arrest, and improved cell viability, DNA synthesis, mitochondrial respiration and antioxidant function. Third, alpha-ketoglutarate enhanced tricarboxylic acid cycle activity, mitochondrial respiration, and decrease the intracellular content of reactive oxygen species. Finally, alpha-ketoglutarate stabilized the mitochondrial membrane potential, increased the ratio of Bcl-2/Bax, decreased the release of cytochrome c and activation of caspase-3, thereby prevented cell apoptosis. Altogether, we proposed that alpha-ketoglutarate protects intestinal cells against hydrogen peroxide-induced damage partly via mitochondria dependent pathway. |
format | Online Article Text |
id | pubmed-5650381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56503812017-10-30 Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells Jiang, Qian Liu, Gang Wang, Xiuqi Hou, Yongqing Duan, Yehui Wu, Guoyao Yin, Yulong Yao, Kang Oncotarget Research Paper Alpha-ketoglutarate, a key intermediate in the Krebs cycle, has been reported to benefit intestinal health. We tested whether alpha-ketoglutarate can protect intestinal cells against hydrogen peroxide induced damage and aimed to reveal the underlying mechanism. Intestinal porcine epithelial cell line J2 were cultured in Dulbecco’s Modified Eagle Medium-High glucose with or without alpha-ketoglutarate and hydrogen peroxide. Cell viability, proliferation, mitochondrial respiration, mitochondrial membrane potential, antioxidant function, apoptosis and mitochondrial-dependent apoptotic pathways were determined. Our experiments demonstrated that, first, exposure to 100μM hydrogen peroxide decreased cell viability, DNA synthesis, mitochondrial respiration and antioxidant function, and increased apoptosis. Second, 2mM alpha-ketoglutarate addition attenuated hydrogen peroxide-induced cell cycle arrest, and improved cell viability, DNA synthesis, mitochondrial respiration and antioxidant function. Third, alpha-ketoglutarate enhanced tricarboxylic acid cycle activity, mitochondrial respiration, and decrease the intracellular content of reactive oxygen species. Finally, alpha-ketoglutarate stabilized the mitochondrial membrane potential, increased the ratio of Bcl-2/Bax, decreased the release of cytochrome c and activation of caspase-3, thereby prevented cell apoptosis. Altogether, we proposed that alpha-ketoglutarate protects intestinal cells against hydrogen peroxide-induced damage partly via mitochondria dependent pathway. Impact Journals LLC 2017-08-24 /pmc/articles/PMC5650381/ /pubmed/29088826 http://dx.doi.org/10.18632/oncotarget.20426 Text en Copyright: © 2017 Jiang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jiang, Qian Liu, Gang Wang, Xiuqi Hou, Yongqing Duan, Yehui Wu, Guoyao Yin, Yulong Yao, Kang Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title | Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title_full | Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title_fullStr | Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title_full_unstemmed | Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title_short | Mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
title_sort | mitochondrial pathway is involved in the protective effects of alpha-ketoglutarate on hydrogen peroxide induced damage to intestinal cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650381/ https://www.ncbi.nlm.nih.gov/pubmed/29088826 http://dx.doi.org/10.18632/oncotarget.20426 |
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