PMID- 29498661 OWN - NLM STAT- MEDLINE DCOM- 20180816 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 3 DP - 2018 Mar 2 TI - The Regulatory Role of MeAIB in Protein Metabolism and the mTOR Signaling Pathway in Porcine Enterocytes. LID - 10.3390/ijms19030714 [doi] LID - 714 AB - Amino acid transporters play an important role in cell growth and metabolism. MeAIB, a transporter-selective substrate, often represses the adaptive regulation of sodium-coupled neutral amino acid transporter 2 (SNAT2), which may act as a receptor and regulate cellular amino acid contents, therefore modulating cellular downstream signaling. The aim of this study was to investigate the effects of MeAIB to SNAT2 on cell proliferation, protein turnover, and the mammalian target of rapamycin (mTOR) signaling pathway in porcine enterocytes. Intestinal porcine epithelial cells (IPEC)-J2 cells were cultured in a high-glucose Dulbecco's modified Eagle's (DMEM-H) medium with 0 or 5 mmoL/L System A amino acid analogue (MeAIB) for 48 h. Cells were collected for analysis of proliferation, cell cycle, protein synthesis and degradation, intracellular free amino acids, and the expression of key genes involved in the mTOR signaling pathway. The results showed that SNAT2 inhibition by MeAIB depleted intracellular concentrations of not only SNAT2 amino acid substrates but also of indispensable amino acids (methionine and leucine), and suppressed cell proliferation and impaired protein synthesis. MeAIB inhibited mTOR phosphorylation, which might be involved in three translation regulators, EIF4EBP1, IGFBP3, and DDIT4 from PCR array analysis of the 84 genes related to the mTOR signaling pathway. These results suggest that SNAT2 inhibition treated with MeAIB plays an important role in regulating protein synthesis and mTOR signaling, and provide some information to further clarify its roles in the absorption of amino acids and signal transduction in the porcine small intestine. FAU - Tang, Yulong AU - Tang Y AD - Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. tangyulong@isa.ac.cn. AD - Hunan Co-Innovation Center of Animal Production Safety (CICAPS), Changsha 410128, China. tangyulong@isa.ac.cn. FAU - Tan, Bie AU - Tan B AD - Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. bietan@isa.ac.cn. AD - Department of Nutrition, University of California, Davis, CA 95616, USA. bietan@isa.ac.cn. FAU - Li, Guangran AU - Li G AD - Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. liguangran@anschina.cn. FAU - Li, Jianjun AU - Li J AD - Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. jianjunli@isa.ac.cn. FAU - Ji, Peng AU - Ji P AUID- ORCID: 0000-0002-7447-5688 AD - Department of Nutrition, University of California, Davis, CA 95616, USA. penji@ucdavis.edu. FAU - Yin, Yulong AU - Yin Y AD - Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China. yinyulong@isa.ac.cn. LA - eng PT - Journal Article DEP - 20180302 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Amino Acid Transport System A) RN - 0 (Amino Acid Transport Systems) RN - 0 (Amino Acids) RN - 0 (Proteins) RN - 11P2JDE17B (beta-Alanine) RN - 19036-43-2 (2,2-dimethyl-beta-alanine) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Amino Acid Transport System A/metabolism MH - Amino Acid Transport Systems MH - Amino Acids/metabolism MH - Animals MH - Cell Line MH - Cell Proliferation/drug effects MH - Cyclic AMP/metabolism MH - Enterocytes/*drug effects/*metabolism MH - Gene Expression Profiling MH - Intracellular Space/metabolism MH - Phosphorylation MH - Protein Biosynthesis MH - Proteins/*metabolism MH - Proteolysis MH - Signal Transduction/*drug effects MH - Swine MH - TOR Serine-Threonine Kinases/*metabolism MH - beta-Alanine/*analogs & derivatives/pharmacology PMC - PMC5877575 OTO - NOTNLM OT - mTOR OT - porcine enterocytes OT - protein turnover OT - sodium-coupled neutral amino acid transporter 2 COIS- The authors declare no conflict of interest. EDAT- 2018/03/03 06:00 MHDA- 2018/08/17 06:00 PMCR- 2018/03/01 CRDT- 2018/03/03 06:00 PHST- 2018/01/03 00:00 [received] PHST- 2018/02/20 00:00 [revised] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/03/03 06:00 [entrez] PHST- 2018/03/03 06:00 [pubmed] PHST- 2018/08/17 06:00 [medline] PHST- 2018/03/01 00:00 [pmc-release] AID - ijms19030714 [pii] AID - ijms-19-00714 [pii] AID - 10.3390/ijms19030714 [doi] PST - epublish SO - Int J Mol Sci. 2018 Mar 2;19(3):714. doi: 10.3390/ijms19030714.