Sigma receptor 1 modulates ER stress and Bcl2 in murine retina.

ABSTRACT: Sigma receptor 1 (?R1), a non-opiate 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 ?R1 have been used in in vitro and in vivo models of retinal cell death. Mice lacking ?R1 (?R1(-/-)) manifest late-onset loss of retinal ganglion cells and retinal electrophysiological changes (after many months). The role of ?R1 in the retina and the mechanisms by which its ligands afford neuroprotection are unclear. We therefore used ?R1(-/-) mice to investigate the expression of ER stress genes (BiP/GRP78, Atf6, Atf4, Ire1?) 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 ?R1(-/-) retina concomitantly with decreases in NFkB and pERK1/2. We postulate that ?R1 regulates ER stress in retinal Müller cells and that the role of ?R1 in retinal neuroprotection probably involves BCL2 and some of the proteins that modify its expression (such as ERK, NF?B). Data from the analysis of the retinal transcriptome of ?R1 null mice provide new insights into the role of ?R1 in retinal neuroprotection.

SUBMITTER: Ha Y 

PROVIDER: S-EPMC3976706 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature