Oxidative modification of lens crystallins by H2O2 and chelated iron.
Crystallins are the soluble structural proteins that constitute approximately 90% of the dry mass of the eye lens. The present study attempts to elucidate possible mechanisms whereby the H2O2 present in the eye could contribute to the oxidative modification of lens crystallins. The data indicate that exposure of solutions of crystallins to H2O2 and EDTA-chelated iron leads to covalent crosslinking of polypeptides, loss of intrinsic protein fluorescence, and the generation of a novel fluorophor emitting in the 420 nm range. These changes closely mimic oxidative modifications that occur in lens proteins in vivo. Exposure of the proteins to H2O2 in the absence of chelated iron failed to generate detectable levels of these modifications. These findings are contrasted with earlier studies of lenses in organ culture where H2O2 alone produced marked damage while the further addition of chelated iron protected the lenses from oxidation.
Zigler
J S
JS
Laboratory of Mechanisms of Ocular Disease, National Eye Institute, Bethesda, MD 20892.
Huang
Q L
QL
Du
X Y
XY
D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000187:drug effects* / Q000378:metabolism; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006878:Hydroxides / Q000494:pharmacology; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013050:Spectrometry, Fluorescence
D003459:Crystallins; D005609:Free Radicals; D006878:Hydroxides; D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide