Abstract
Some quinones catalyze superoxide formation in a futile cycle involving electron transfer to molecular oxygen. If the quinolic precursors of melanin participated in the futile cycle, the high ambient oxygen surrounding postnatal RPE would make continued melanogenesis risky for the retina. To probe the possibility that arrest of melanogenesis in postnatal RPE is a protective mechanism, we assayed the growth rates of RPE cells, aortic endothelial cells and skin fibroblasts exposed to 0, 10, 50, 100 and 250 μ m dopa. To assess the contribution of the futile cycle, we studied the effects of oxygen concentration and the antioxidants, superoxide dismutase and catalase. We found that all three cell types were significantly and dose-dependently inhibited by dopa and that the effects of dopa were oxygen dependent. The powerful inhibition of RPE cells by dopa was counteracted by inclusion of superoxide dismutase and catalase, but not by an inhibitor of dopa oxidase (phenylthiourea), indicating that the mechanism of growth suppression did not involve melanogenesis but, rather, dopa-dependent formation of superoxide in the media. Endothelial cells were more sensitive to the dopa-mediated oxidative damage than were RPE cells or fibroblasts. Fibroblasts were most affected by oxygen alone, and least affected by dopa. These data suggest that suppression of melanogenesis in the postnatal RPE may be an important mechanism for preventing oxidative damage to the retina and the choriocapillaris. We propose that the generation of oxygen radicals by the quinone futile cycle is a viable model of the damage of cells in culture by dopa.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.