Pro-oxidant activation of ocular reductants. 2. Lens epithelial cell cytotoxicity of a dietary quinone is associated with a stable free radical formed with glutathione in vitro.
The ability of 2,6-dimethoxyquinone (DMQ) to impair 86Rb uptake by bovine lens epithelial cells was found to be independent of exogenous ascorbate in contrast to the impairment induced by Fe/Cu or riboflavin plus light. The cytotoxicity was associated with an electron spin resonance (ESR) detectable singlet radical (g = 2.0062) which also formed on incubation of DMQ with glutathione (GSH) or gamma-crystallin in vitro. Formation of the stable free radical appeared to require conjugation of DMQ by peptidyl thiol and required transition metal catalysis. A structure for the DMQ-glutathione free radical conjugate is proposed. Redox activity of quinone conjugates is suggested to be of relevance to an oxidative damage hypothesis of cataract.
Wolff
S P
SP
Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Spector
A
A
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D016227:Benzoquinones; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D004578:Electron Spin Resonance Spectroscopy; D004848:Epithelium / Q000187:drug effects; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011809:Quinones / Q000494:pharmacology*
D016227:Benzoquinones; D005609:Free Radicals; D011809:Quinones; C030511:2,6-dimethoxy-1,4-benzoquinone; D005978:Glutathione; D001205:Ascorbic Acid