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Int. J. Mol. Sci. 2017, 18(12), 2617; https://doi.org/10.3390/ijms18122617

l-Glutamine Attenuates Apoptosis Induced by Endoplasmic Reticulum Stress by Activating the IRE1α-XBP1 Axis in IPEC-J2: A Novel Mechanism of l-Glutamine in Promoting Intestinal Health

1,2
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1,3
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1,2
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1,3,* , 1,3,4,* and 1,3,4
1
Key Laboratory of Agroecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Changsha 410125, China
2
University of the Chinese Academy of Sciences, Beijing 10008, China
3
College of Animal Science and Technology, Hunan Agricultural University, Changsha 410125, China
4
Hunan Co-Innovation Center of Animal Production Safety, CICAPS, Changsha 410128, China
*
Authors to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 28 November 2017 / Accepted: 1 December 2017 / Published: 5 December 2017
(This article belongs to the Special Issue Amino Acids Transport and Metabolism)
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Abstract

Intestinal absorption and barrier malfunctions are associated with endoplasmic reticulum stress (ERS) in the intestine. We induced ERS by exposing the intestinal porcine epithelial cell line J2 (IPEC-J2) to tunicamycin (TUNI) to explore the potential of l-glutamine to reduce ERS-induced apoptosis. Our experiments demonstrated that exposing cells to TUNI results in spontaneous ERS and encourages the upregulation of glucose-regulated protein 78 (GRP78). Prolonged TUNI-induced ERS was found to increase apoptosis mediated by C/enhancer binding protein homologous protein (CHOP), accompanied by GRP78 downregulation. Treatment with l-glutamine was found to promote cell proliferation within the growth medium but to have little effect in basic Dulbecco’s modified Eagle medium. Finally, in the milieu of TUNI-induced ERS, l-glutamine was found to maintain a high level of GRP78, alleviate CHOP-mediated apoptosis and activate the inositol requiring enzyme 1α (IRE1α)-X-box binding protein 1 (XBP1) axis. A specific inhibitor of the IRE1α-XBP1 axis reversed the protective effect of l-glutamine by blocking the expression of IRE1α/XBP1s. We propose that the functional effect of l-glutamine on intestinal health may be partly due to its modulation of ERS and CHOP-mediated apoptosis. View Full-Text
Keywords: endoplasmic reticulum stress; IRE1α-XBP1; l-glutamine; intestinal porcine epithelial cell line J2 endoplasmic reticulum stress; IRE1α-XBP1; l-glutamine; intestinal porcine epithelial cell line J2
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Jiang, Q.; Chen, J.; Liu, S.; Liu, G.; Yao, K.; Yin, Y. l-Glutamine Attenuates Apoptosis Induced by Endoplasmic Reticulum Stress by Activating the IRE1α-XBP1 Axis in IPEC-J2: A Novel Mechanism of l-Glutamine in Promoting Intestinal Health. Int. J. Mol. Sci. 2017, 18, 2617.

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