期刊
ONCOTARGET
卷 8, 期 43, 页码 74820-74835出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.20426
关键词
alpha-ketoglutarate; oxidative damage; cell apoptosis; mitochondrial respiration; intestinal porcine epithelial cells
资金
- National Science Foundation for Distinguished Young Scholars of Hunan Province [2016JJ1015]
- Key Programs of frontier scientific research of the Chinese Academy of Sciences
- National Basic Research Program of China [2013CB127306]
- Open Foundation of Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences [ISA2016101]
- Chinese Academy of Sciences Hundred Talent award
- National Natural Science Foundation Project [31472107]
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 100 mu M 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.
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