| First Author | Ha Y | Year | 2014 |
| Journal | Cell Tissue Res | Volume | 356 |
| Issue | 1 | Pages | 15-27 |
| PubMed ID | 24469320 | Mgi Jnum | J:321034 |
| Mgi Id | MGI:6862445 | Doi | 10.1007/s00441-013-1774-8 |
| Citation | Ha Y, et al. (2014) Sigma receptor 1 modulates ER stress and Bcl2 in murine retina. Cell Tissue Res 356(1):15-27 |
| abstractText | Sigma receptor 1 (sigmaR1), 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 sigmaR1 have been used in in vitro and in vivo models of retinal cell death. Mice lacking sigmaR1 (sigmaR1(-/-)) manifest late-onset loss of retinal ganglion cells and retinal electrophysiological changes (after many months). The role of sigmaR1 in the retina and the mechanisms by which its ligands afford neuroprotection are unclear. We therefore used sigmaR1(-/-) mice to investigate the expression of ER stress genes (BiP/GRP78, Atf6, Atf4, Ire1alpha) 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 Muller glial cells. BCL2 levels decreased in sigmaR1(-/-) retina concomitantly with decreases in NFkB and pERK1/2. We postulate that sigmaR1 regulates ER stress in retinal Muller cells and that the role of sigmaR1 in retinal neuroprotection probably involves BCL2 and some of the proteins that modify its expression (such as ERK, NFkappaB). Data from the analysis of the retinal transcriptome of sigmaR1 null mice provide new insights into the role of sigmaR1 in retinal neuroprotection. |
