TY - JOUR
T1 - Sigma receptor 1 modulates ER stress and Bcl2 in murine retina
AU - Ha, Yonju
AU - Shanmugam, Arul K.
AU - Markand, Shanu
AU - Zorrilla, Eric
AU - Ganapathy, Vadivel
AU - Smith, Sylvia B.
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health, R01 EY014560. Y.Ha.A.K.Shanmugam.S.Markand.S.B.Smith(*) Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, 1120 15th Street, CB 1101, Augusta GA 30912-2000, USA e-mail: [email protected]
PY - 2014/4
Y1 - 2014/4
N2 - Sigma receptor 1 (σR1), 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 σR1 have been used in in vitro and in vivo models of retinal cell death. Mice lacking σR1 (σR1 -/-) manifest late-onset 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.
AB - Sigma receptor 1 (σR1), 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 σR1 have been used in in vitro and in vivo models of retinal cell death. Mice lacking σR1 (σR1 -/-) manifest late-onset 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.
KW - Endoplasmic reticulum stress
KW - Mouse
KW - Müller cells
KW - Retinal disease
KW - Retinal neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=84898883066&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898883066&partnerID=8YFLogxK
U2 - 10.1007/s00441-013-1774-8
DO - 10.1007/s00441-013-1774-8
M3 - Article
C2 - 24469320
AN - SCOPUS:84898883066
SN - 0302-766X
VL - 356
SP - 15
EP - 27
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 1
ER -