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Int. J. Mol. Sci. 2015, 16(7), 16275-16287; doi:10.3390/ijms160716275

Experimental Evidence Shows Salubrinal, an eIF2α Dephosphorylation Inhibitor, Reduces Xenotoxicant-Induced Cellular Damage

Department of Hygiene and Public Health I, Tokyo Women's Medical University, Tokyo 162-8666, Japan
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Academic Editor: Hansruedi Glatt
Received: 18 May 2015 / Revised: 30 June 2015 / Accepted: 10 July 2015 / Published: 17 July 2015
(This article belongs to the Special Issue Modulators of Endoplasmic Reticulum Stress)
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Abstract

Accumulating evidence indicates that endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR) are involved in the pathogenesis of not only the protein misfolding disorders such as certain neurodegenerative and metabolic diseases, but also in the cytotoxicity of environmental pollutants, industrial chemicals, and drugs. Thus, the modulation of ER stress signaling pathways is an important issue for protection against cellular damage induced by xenotoxicants. The substance salubrinal has been shown to prevent dephosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α). The phosphorylation of eIF2α appears to be cytoprotective during ER stress, because inhibition of the translation initiation activity of eIF2α reduces global protein synthesis. In addition, the expression of activating transcription factor 4 (ATF4), a transcription factor that induces the expression of UPR target genes, is up-regulated through alternative translation. This review shows that salubrinal can protect cells from the damage induced by a wide range of xenotoxicants, including environmental pollutants and drugs. The canonical and other possible mechanisms of cytoprotection by salubrinal from xenotoxicant-induced ER stress are also discussed. View Full-Text
Keywords: apoptosis; ATF4; cytoprotection; drugs; eIF2α; environmental pollutants; ER stress; salubrinal; xenotoxicants apoptosis; ATF4; cytoprotection; drugs; eIF2α; environmental pollutants; ER stress; salubrinal; xenotoxicants
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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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Matsuoka, M.; Komoike, Y. Experimental Evidence Shows Salubrinal, an eIF2α Dephosphorylation Inhibitor, Reduces Xenotoxicant-Induced Cellular Damage. Int. J. Mol. Sci. 2015, 16, 16275-16287.

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