zeta-Crystallin catalyzes the reductive activation of 2,4,6-trinitrotoluene to generate reactive oxygen species: a proposed mechanism for the induction of cataracts

Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction o f cataract in which oxidative stress plays a critical role, From bovine len s we purified to homogeneity and identified an enzyme that catalyzes the re duction of TNT, resulting in the production of reactive oxygen species. The final preparation of TNT reductase showed a single band with a subunit mol ecular weight of 38 kDa on SDS-PAGE, Sequence data from peptides obtained b y digestion with lysylendopeptidase Achromobacter protease I(API) revealed that TNT reductase is identical to zeta-crystallin. Superoxide anions were formed during reduction of TNT by zeta-crystallin, though negligible enzyme activity or protein content for superoxide dismutase, a superoxide scaveng ing enzyme, was found in the lens. Thus, the present results suggest that t he induction of cataracts by TNT may be associated with increased oxidative stress, as a result of reductive activation of TNT generating superoxide a nions, there being minimal antioxidant enzyme activity for defense against reactive oxygen species exogenously produced in the lens. (C) 2000 Federati on of European Biochemical Societies. Published by Elsevier Science B.V. Al l rights reserved.