Resveratrol stimulates mitochondrial bioenergetics to protect retinal pigment epithelial cells from oxidative damage.

PURPOSE: Resveratrol (RSV) alleviates oxidative damage in human adult retinal pigment epithelial (ARPE) cells. Mitochondrial bioenergetics is associated with oxidative stress. The purpose of this study was to examine the role of mitochondrial bioenergetics in the cytoprotective effect of RSV. Its role in protection against the adverse effects of cigarette smoke (CS) in experimental choroidal neovascularization (CNV) was also examined. METHODS: Cultured ARPE-19 cells were treated with acrolein alone or acrolein with added RSV. Temporal changes in cell viability, expression of the antioxidant protein, and mitochondrial bioenergetics were evaluated. In an animal study, CNV lesions were created in Brown Norway rats by laser-induced photocoagulation. Effects of CS alone or with additional RSV treatment on CNV lesions were quantified by fundus fluorescein angiography. RESULTS: In ARPE-19 cells, RSV rescued acrolein-induced cell death, alongside reversal of acrolein-induced superoxide dismutase expression. Resveratrol increased the mitochondrial bioenergetics, including basal respiratory rate, adenosine triphosphate synthesis via oxidative phosphorylation, and maximal mitochondrial capacity. In animal experiments, CS induced a significant increase in CNV following laser injury, and this increase in CNV was appreciably prevented following peripheral infusion of RSV. CONCLUSIONS: Our results indicate that RSV, a major polyphenol found in red wine, exerts protection against acrolein-induced cytotoxicity in human ARPE-19 cells via increases in the mitochondrial bioenergetics. In addition, the antioxidant effect of RSV may contribute to protection against laser-induced CNV in animals exposed to CS. Therefore, RSV might be beneficial for treatment of acrolein-induced or CS-evoked RPE degeneration.

Up-regulation of glutamate receptors in nucleus tractus solitarii underlies potentiation of baroreceptor reflex by heat shock protein 70.

Whereas induction of the 70-kDa heat shock protein (HSP70) in the nucleus tractus solitarii (NTS), the terminal site in the brain stem for primary baroreceptor afferents, augments baroreceptor reflex (BRR) response, the underlying cellular and molecular mechanism is essentially unexplored. In Sprague-Dawley rats, we evaluated the hypothesis that HSP70 may potentiate BRR response by up-regulating the molecular synthesis and functional expression of glutamate receptors in the NTS. Animals subjected to brief hyperthermic heat shock (HS; 42 degrees C for 15 min) exhibited augmented expression of NR1 or NR2A subunit of N-methyl-D-aspartate (NMDA) receptors, GluR1 or GluR4 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors and KA1 subunit of kainate receptors in the NTS. Intriguingly, this up-regulation of glutamate receptors was preceded by an increase in HSP70 expression at the NTS. The HS-induced augmentation in responsiveness of barosensitive NTS neurons to transient hypertension or potentiation of BRR response was discernibly blunted by MK-801 or 6-cyano-7-nitroquinoxaline-2,3-dione. Bilateral microinjection into the NTS of an antisense hsp70 oligonucleotide (50 pmol) before HS significantly suppressed the induced expression of HSP70 or the increase in glutamate receptor subunits in the dorsal medulla and discernibly attenuated the potentiation of BRR response. Control microinjection into the NTS of sense or scrambled hsp70 oligonucleotide (50 pmol) was ineffective. These findings suggest that HSP70 induced by HS may enhance BRR response by up-regulating the molecular synthesis and functional expression of NR1 or NR2A subunit of NMDA receptors and GluR1, GluR4, or KA1 subunit of non-NMDA receptors in the NTS.