Carnitine protects the molecular chaperone activity of lens α-crystallin and decreases the posttranslational protein modifications induced by oxidative stress

alpha-Crystallin prevents heat-induced lens protein aggregation by acting as a molecular chaperone. We investigated whether oxidative stress in an in vitro model of cataract increases the posttranslational modifications to lens proteins induced by transglutaminase (TGase). We also investigated whether carnitine safeguards the chaperone activity of alpha-crystallin and inhibits the TGase-mediated aggregation of lens proteins and lens opacification. One lens of each pair of rat lenses was cultured without H2O2 (controls), and the controlateral lens was exposed to 500 muM H2O2, an as oxidizing agent, in the presence and absence of 300 muM L-carnitine. Lenses treated with H2O2 alone became opaque, whereas the L-carnitine-treated lenses remained clear. Incubation with 500 muM H2O2 significantly increased the level of TGase-mediated cross-links of lens protein and decreased the ability of a-crystallin to prevent heat-induced aggregation of beta(L)-crystallin, L-carnitine prevented both these negative effects. After H2O2, glutathione and free carnitine levels dropped dramatically. L-carnitine did not prevent the loss of glutathione, but it did prevent carnitine from falling below control values. In conclusion, carnitine safeguards the chaperone activity of alpha-crystallin that prevents protein aggregation in the lens, and it decreases the protein posttranslational modifications induced by oxidative stress. This process is not mediated by glutathione.