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The Regulatory Role of MeAIB in Protein Metabolism and the mTOR Signaling Pathway
in Porcine Enterocytes
#MMPMID29498661
Tang Y
; Tan B
; Li G
; Li J
; Ji P
; Yin Y
Int J Mol Sci
2018[Mar]; 19
(3
): ? PMID29498661
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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.
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