Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells

文献类型： 外文期刊

第一作者： Yao, Kang

作者： Yao, Kang;Yin, Yulong;Wu, Guoyao;Yao, Kang;Yin, Yulong;Wu, Guoyao;Yao, Kang;Li, Xilong;Xi, Pengbin;Wang, Junjun;Lei, Jian;Wu, Guoyao;Xi, Pengbin;Wang, Junjun;Wu, Guoyao;Hou, Yongqing

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关键词： a-Ketoglutarate;Intestinal cells;mTOR signaling;Protein synthesis

期刊名称：AMINO ACIDS （ 影响因子：3.52； 五年影响因子：3.6 ）

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收录情况： SCI

摘要： a-Ketoglutarate (AKG) is a key intermediate in glutamine metabolism. Emerging evidence shows beneficial effects of AKG on clinical and experimental nutrition, particularly with respect to intestinal growth and integrity. However, the underlying mechanisms are unknown. Intestinal porcine epithelial cells (IPEC-1) were used to test the hypothesis that AKG inhibits glutamine degradation and enhances protein synthesis. IPEC-1 cells were cultured for 3 days in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 0, 0.2, 0.5 or 2 mM of AKG. At the end of the 3-day culture, cells were used to determine L-[U-~(14)C]glutamine utilization, protein concentration, protein synthesis, and the total and phosphorylated levels of the mammalian target of the rapamycin (mTOR), ribosomal protein S6 kinase-1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1). Compared with 0 mM of AKG (control), 0.2 and 0.5 mM of AKG dose-dependently reduced (P < 0.05) glutamine degradation and the production of glutamate, alanine and aspartate in IPEC-1 cells. Addition of 0.5 and 2 mM of AKG to culture medium enhanced protein synthesis (P < 0.05) by 78 and 101% without affecting protein degradation, compared to the control group. Rapamycin (50 nM; a potent inhibitor of mTOR) attenuated the stimulatory effect of AKG on protein synthesis. Consistent with these metabolic data, the addition of 0.5 or 2 mM of AKG to culture medium increased (P < 0.05) the phosphorylated levels of mTOR, S6kl and 4E-BP1 proteins. Collectively, these results indicate that AKG can spare glutamine and activate the mTOR signaling pathway to stimulate protein synthesis in intestinal epithelial cells.

分类号： Q5

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