Cataract induced by exposure to naphthalene is thought to mainly involve its metabolic activation, forming 1,2-naphthoquinone (1,2-NQ), which can modify proteins through chemical modifications. In the present study, we examined the effect of 1,2-NQ on aggregation of crystallins (cry) associated with cataract. Incubation of bovine β-cry with 1,2-NQ caused covalent modification of β-cry at Cys117 and Lys125 accompanied by reduction in its thiol content, resulting in a concentration- and temperature-dependent aggregation of β-cry, whereas only little aggregation of α-cry induced by 1,2-NQ was seen. Interestingly, addition of α-cry to the reaction mixture of β-cry and 1,2-NQ markedly blocked β-cry aggregation induced by 1,2-NQ in a concentration-dependent manner. These results suggest that β-cry predominantly undergoes chemical modification by 1,2-NQ, causing its aggregation, which is suppressed by the chaperone-like protein, α-cry. This β-cry aggregation may be, at least in part, involved in the induction of cataract caused by 1,2-NQ.
Keywords: 1,2-Naphthoquinone; Aggregation; Chaperone; Covalent modification; Crystalline.