l-Glutamine deprivation induces autophagy and alters the mTOR and MAPK signaling pathways in porcine intestinal epithelial cells
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L-Glutamine (Gln) is an essential amino acid for intestinal growth and integrity. However, the underlying molecular mechanisms are not fully known. In the present study, porcine intestinal epithelial cells (IPEC-1) were used to test the hypothesis that autophagy is induced by Gln deprivation and inhibited by Gln supplementation. After a 2-day period of growth in normal medium, IPEC-1 cells were transferred to a Gln-free custom-made DMEM. Cell numbers, the distribution of autophagosomes, the abundance of the protein for an autophagy marker LC3B, as well as abundances of the mTOR and MAPK proteins during an 8-h period were determined. Furthermore, the rescue effect of 5 mM Gln was evaluated. Our results showed that Gln deprivation reduced the cell number, while enhancing the accumulation of autophagosomes and the expression of LC3B-II in IPEC-1 cells within 8 h. The concentrations of Glu, Asp, Cit, Arg, Leu, Ile, Val, Ala, β-Ala, Orn, Phe, Met and Ser in the culture medium were altered by Gln deprivation. Further analysis revealed that Gln deficiency inactivated, but Gln supplementation activated, the mTOR and MAPK/ERK signaling pathways. Collectively, our findings support the notion that Gln deficiency induces autophagy and disturbs amino acid metabolism in intestinal epithelial cells, as well as attenuated their mTOR and MAPK/ERK signaling pathways to inhibit protein synthesis and cell proliferation.
author list (cited authors)
Zhu, Y., Lin, G., Dai, Z., Zhou, T., Li, T., Yuan, T., ... Wang, J.