Sigma receptor ligands protect human retinal cells against oxidative stress.
This study was undertaken to investigate the role of sigma receptors during the oxidative damage on human retinal pigment epithelial cells, and to assess whether sigma receptor ligands enhance survival and protect DNA of cells challenged by oxidative stress. Pretreatment with PRE-084, a sigma1 receptor agonist, resulted in significant increased viability in a dose-related manner. DNA damage induced by oxidative insult was significantly lower with PRE-084. The effects of PRE-084 were antagonized by pretreatment with sigma1 receptor antagonists (NE-100 and BD1047), but interestingly were synergized by cotreatment with BD1047 that also presented an affinity for the sigma2 receptor. The results suggest that sigma1 receptors play an important role against retinal damage, even though sigma2 receptor involvement cannot be excluded.
Bucolo
Claudio
C
Department of Experimental and Clinical Pharmacology, School of Medicine, University of Catania, Catania, Italy. bucocla@unict.it
Drago
Filippo
F
Lin
Li-Ren
LR
Reddy
Venkat N
VN
D000840:Anisoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects*; D005029:Ethylenediamines / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D009025:Morpholines / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011437:Propylamines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012160:Retina / Q000166:cytology*
D000840:Anisoles; D005029:Ethylenediamines; D009025:Morpholines; D011437:Propylamines; D017480:Receptors, sigma; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D006861:Hydrogen Peroxide