L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK.
L-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK.
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L-谷氨酰胺通过独立于 AMPK 激活 mTOR 信号通路来增强肠细胞生长
DOI：
10.1007/s00726-014-1842-8
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Wu Guoyao
中科院分区：
文献类型：
--
作者：
Yi Dan;Hou Yongqing;Wang Lei;Ouyang Wanjin;Long Minhui;Zhao Di;Ding Binying;Liu Yulan;Wu Guoyao
Neonates (including human infants) requirel-glutamine (Gln) for optimal intestinal health. This study tested the hypothesis that Gln enhances enterocyte growth via both mammalian target of rapamycin (mTOR) and AMP-activated kinase (AMPK) signaling pathways. Intestinal porcine epithelial cells (IPEC-1) were cultured for 3 days in Gln-free Dulbecco’s modified Eagle medium containing 0 or 2 mM Gln. To determine the role of mTOR and AMPK on cell growth, additional experiments were conducted where medium contained 2 mM Gln and 10 nM rapamycin (Rap, an inhibitor of mTOR) or 1 μM compound C (an inhibitor of AMPK). IPEC-1 cell growth increased with increasing concentrations of Gln from 0 to 2 mM. Compared with 0 mM Gln, 2 mM Gln increased (P< 0.05) the amounts of phosphorylated 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (p70S6 kinase) proteins but did not affect abundances of total or phosphorylated AMPK protein. Gln also increased mRNA levels for Bcl-2, mTOR, p70S6 kinase, 4E-BP1, COX7C, ASCT2, ODC, SGLT-1, CFTR, Na+/K+-ATPase, HSP70, and ZO-1. Similarly, cells cultured with Rap and Gln exhibited higher (P< 0.05) abundances of phosphorylated 4E-BP1 and p70S6 kinase proteins than the Rap-only group, whereas abundances of phosphorylated mTOR and 4E-BP1 proteins were increased when AMPK was inhibited by compound C. Conversely, the amount of phosphorylated AMPK increased when mTOR was inhibited by Rap, suggesting a negative cross-talk between mTOR and AMPK. Collectively, these results indicate that Gln stimulates enterocyte growth by activating the mTOR signaling pathway independently of AMPK.
