Neuroactive steroids protect retinal pigment epithelium against oxidative stress

被引:20
作者
Bucolo, C [1 ]
Drago, F
Lin, LR
Reddy, VN
机构
[1] Univ Catania, Sch Med, Dept Expt & Clin Pharmacol, I-95125 Catania, Italy
[2] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA
关键词
neuroactive steroids; oxidative stress; retinal pigment epithelial cells; sigma(1)receptors;
D O I
10.1097/00001756-200508010-00014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
This study was undertaken to assess whether neuroactive steroids, 17 beta-estradiol and dehydroepiandrosterone-sulfate, enhance survival and protect DNA of human retinal pigment epithelial cells challenged by oxidative stress, and to investigate the role of sigma(1) receptors in the effects of neuroactive steroids. Retinal pigment epithelial cells were treated with various concentrations of neuroactive steroids and then exposed to hydrogen peroxide. Pretreatment with steroids resulted in significant increased viability in a dose-related manner. DNA damage induced by oxidative insult was significantly lower with steroid pretreatment. The effects of 17 beta-estradiol and dehydroepiandrosterone-sulfate were antagonized by pretreatment with a a, receptor antagonist. The results suggest that neuroactive steroids protect retinal cells from oxidative stress, and that this effect is mediated by sigma(1) receptors.
引用
收藏
页码:1203 / 1207
页数:5
相关论文
共 22 条
[1]   Hydrogen peroxide causes significant mitochondrial DNA damage in human RPE cells [J].
Ballinger, SW ;
Van Houten, B ;
Jin, GF ;
Conklin, CA ;
Godley, BF .
EXPERIMENTAL EYE RESEARCH, 1999, 68 (06) :765-772
[2]   Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage [J].
Bastianetto, S ;
Ramassamy, C ;
Poirier, J ;
Quirion, R .
MOLECULAR BRAIN RESEARCH, 1999, 66 (1-2) :35-41
[3]   17-BETA ESTRADIOL PROTECTS NEURONS FROM OXIDATIVE STRESS-INDUCED CELL-DEATH IN-VITRO [J].
BEHL, C ;
WIDMANN, M ;
TRAPP, T ;
HOLSBOER, F .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 216 (02) :473-482
[4]   Effects of neurosteroids on ischemia-reperfusion injury in the rat retina:: role of σ1 recognition sites [J].
Bucolo, C ;
Drago, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 498 (1-3) :111-114
[5]  
Cao W, 2003, ADV EXP MED BIOL, V533, P395
[6]  
Crawford KW, 2002, CANCER RES, V62, P313
[7]  
DELOORE KL, 1994, NEUROSCI RES COMMUN, V14, P43
[8]  
GARG TK, 2003, BMC OPHTHALMOL
[9]   Purification, molecular cloning, and expression of the mammalian sigma(1)-binding site [J].
Hanner, M ;
Moebius, FF ;
Flandorfer, A ;
Knaus, HG ;
Striessnig, J ;
Kempner, E ;
Glossmann, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :8072-8077
[10]   Hydrogen peroxide stimulates apoptosis in cultured human retinal pigment epithelial cells [J].
Jin, GF ;
Hurst, JS ;
Godley, BF .
CURRENT EYE RESEARCH, 2001, 22 (03) :165-173