Abstract
We examined the cytoprotective effect of quercetin via activator protein (AP-1) and the heat shock protein 70 (Hsp70) pathway against light-induced retinal degeneration in rats. Quercetin was administered intraperitoneally to Sprague-Dawley rats for seven days before light exposure to intense white fluorescent light (3000 lux) for 24 h. Light-induced retinal damage was determined by the number of rows of photoreceptor cell nuclei, the microstructures of the rod outer segments and retinal pigment epithelium, and terminal deoxynucleotidyl transferase (TdT)-mediated 2′-Deoxyuridine-5′-triphosphate (dUTP) nick end labeling. To elucidate the cytoprotective mechanism of quercetin, expression levels were measured in the rat retinas of 8-hydroxy-deoxyguanosine (8-OHdG), a marker of oxidative stress; Hsp70; and transcription factor AP-1 transcription activity. Pretreatment with quercetin inhibited light-induced photoreceptor cellular apoptosis and subsequent retinal degeneration in rats. 8-OHdG and Hsp70 protein expressions were up-regulated markedly by light exposure and suppressed by quercetin pretreatment. The results of an electrophoretic mobility shift assay showed that AP-1-binding activity was activated by light exposure, and binding of c-Fos and c-Jun, but not JunB, mediated the binding activity. Intraperitoneal administration of quercetin decreases photooxidative damage in the retina and mediates cytoprotection against light-induced photoreceptor cell degeneration in rats. Suppression of the heterodimeric combination of c-Jun and c-Fos proteins at the AP-1 binding site is highly involved in quercetin-mediated cytoprotection.
Highlights
Exposure to excessive light induces apoptotic cellular death of the photoreceptors in albino rats [1,2] and mice [3,4], and reactive oxygen species are important factors in this light-induced apoptosis [5,6]
Quercetin and its metabolites protect against oxidative stress in the rat lens [15] and cultured chick retinal cells [16], human retinal pigment epithelium (RPE) cells [17,18], and bovine retina [19], and prevent lipid peroxidation in bovine and porcine rod outer segments (ROS) [20]
The results indicated that light-induced photoreceptor cell apoptosis and subsequent retinal degeneration were more severe in the quercetin (−) group than in the quercetin (+) group
Summary
Exposure to excessive light induces apoptotic cellular death of the photoreceptors in albino rats [1,2] and mice [3,4], and reactive oxygen species are important factors in this light-induced apoptosis [5,6]. Quercetin and its metabolites are potent antioxidants [11,12], with oxygen radical scavenging. Quercetin and its metabolites protect against oxidative stress in the rat lens [15] and cultured chick retinal cells [16], human retinal pigment epithelium (RPE) cells [17,18], and bovine retina [19], and prevent lipid peroxidation in bovine and porcine rod outer segments (ROS) [20]
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