Increased susceptibility to metal catalysed oxidation of diabetic lens beta L crystallin: possible protection by dietary supplementation with acetylsalicylic acid.
The effect of dietary supplementation with acetylsalicylic acid on the increased modification, and susceptibility to modification, of lens crystallins from the streptozocin diabetic rat, has been determined. This was done by the measurement of characteristic markers of protein post-translational oxidative modification and glycation, in beta L crystallins purified from the lenses of control, diabetic and acetylsalicylic acid-supplemented diabetic animals, with no further manipulations, and again following the application of an in vitro graded oxidative insult. Crystallins prepared from the diabetic, in comparison with control animals, exhibited a higher level of bityrosine- and AGEP-like fluorescence as well as a loss of tryptophan fluorescence and sulphydryl groups. Exposure to an oxidative insult (in the form of CuSO4 and ascorbate) increased all parameters in beta L crystallins, irrespective of their source. However, the effects were most pronounced in the diabetic in which the effects of oxidative stress were always greater than the control crystallin. Dietary supplementation of the diabetic group with acetylsalicylic acid (100 mg kg-1 body weight day-1) had a marked effect in decreasing the level of modification induced in diabetic crystallins, by in vitro metal catalysed oxidative stress, lowering the levels of AGEP- and bityrosine-like fluorescence and carbonyl group formation. Increasing the oxidative stress by addition of increasing concentrations of H2O2, induced stress proportional increases in the indicators of protein modification in all beta L crystallins, irrespective of source. The increase in damage in relation to H2O2 concentration was greater in those crystallins from diabetic animals, revealing a greater susceptibility to such oxidative stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Jones
R H
RH
Department of Biochemistry and Molecular Biology, University College London Medical School, U.K.
Hothersall
J S
JS
D000818:Animals; D001205:Ascorbic Acid; D001241:Aspirin / Q000494:pharmacology*; D002386:Cataract / Q000503:physiopathology; D003300:Copper; D003459:Crystallins / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006861:Hydrogen Peroxide; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D003459:Crystallins; D003300:Copper; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid; D001241:Aspirin