Suppression of Light-Induced Retinal Degeneration by Quercetin via the AP-1 Pathway in Rats.

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.

• Authors: Yasurou Koyama, Sachiko Kaidzu, Yong-Chul Kim, Yotaro Matsuoka, Tomoe Ishihara, Akihiro Ohira, Masaki Tanito
• Journal: Antioxidants (Basel, Switzerland) (Antioxidants (Basel)) Vol. 8 Issue 4 (Mar 27 2019) ISSN: 2076-3921 [Print] Switzerland
• PMID: 30934771 (Publication Type: Journal Article)