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Title of Journal: Cell Tissue Res

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Abbravation: Cell and Tissue Research

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Springer Berlin Heidelberg

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DOI

10.1007/bf00384932

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ISSN

1432-0878

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Sigma receptor 1 modulates ER stress and Bcl2 in m

Authors: Yonju Ha Arul K Shanmugam Shanu Markand Eric Zorrilla Vadivel Ganapathy Sylvia B Smith
Publish Date: 2014/01/28
Volume: 356, Issue: 1, Pages: 15-27
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Abstract

Sigma receptor 1 σR1 a nonopiate transmembrane protein located on endoplasmic reticulum ER and mitochondrial membranes is considered to be a molecular chaperone Marked protection against cell death has been observed when ligands for σR1 have been used in in vitro and in vivo models of retinal cell death Mice lacking σR1 σR1 / manifest lateonset loss of retinal ganglion cells and retinal electrophysiological changes after many months The role of σR1 in the retina and the mechanisms by which its ligands afford neuroprotection are unclear We therefore used σR1 / mice to investigate the expression of ER stress genes BiP/GRP78 Atf6 Atf4 Ire1α and proteins involved in apoptosis BCL2 BAX and to examine the retinal transcriptome at young ages Whereas no significant changes occurred in the expression of major ER stress genes over a period of a year in neural retina marked changes were observed in these genes especially Atf6 in isolated retinal Müller glial cells BCL2 levels decreased in σR1 / retina concomitantly with decreases in NFkB and pERK1/2 We postulate that σR1 regulates ER stress in retinal Müller cells and that the role of σR1 in retinal neuroprotection probably involves BCL2 and some of the proteins that modify its expression such as ERK NFκB Data from the analysis of the retinal transcriptome of σR1 null mice provide new insights into the role of σR1 in retinal neuroprotection

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