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

• Published in: FEBS letters Vol. 478; no. 3; pp. 295 - 298
• Main Authors: Kumagai, Yoshito, Wakayama, Toshihiko, Li, Song, Shinohara, Azusa, Iwamatsu, Akihiro, Sun, Guifan, Shimojo, Nobuhiro
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 04.08.2000
• Subjects: 2,4,6-Trinitrotoluene; Active oxygen; Amino Acid Sequence; Animals; Bovine; Cataract; Cataract - etiology; Cataract - metabolism; Cattle; Crystallins - chemistry; Crystallins - isolation & purification; Crystallins - metabolism; Lens; Lens, Crystalline - enzymology; Lens, Crystalline - metabolism; Models, Biological; Molecular Sequence Data; Molecular Weight; NADP - metabolism; Reactive Oxygen Species - metabolism; Reducing Agents - chemistry; Reducing Agents - isolation & purification; Reducing Agents - metabolism; Superoxide Dismutase - analysis; Superoxides - metabolism; Trinitrotoluene - metabolism; ζ-Crystallin; Cataract; Lens; Active oxygen; Bovine; ζ-Crystallin; 2,4,6-Trinitrotoluene
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(00)01841-X

Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction of cataract in which oxidative stress plays a critical role. From bovine lens we purified to homogeneity and identified an enzyme that catalyzes the reduction of TNT, resulting in the production of reactive oxygen species. The final preparation of TNT reductase showed a single band with a subunit molecular weight of 38 kDa on SDS–PAGE. Sequence data from peptides obtained by digestion with lysylendopeptidase Achromobacter protease I (API) revealed that TNT reductase is identical to ζ-crystallin. Superoxide anions were formed during reduction of TNT by ζ-crystallin, though negligible enzyme activity or protein content for superoxide dismutase, a superoxide scavenging enzyme, was found in the lens. Thus, the present results suggest that the induction of cataracts by TNT may be associated with increased oxidative stress, as a result of reductive activation of TNT generating superoxide anions, there being minimal antioxidant enzyme activity for defense against reactive oxygen species exogenously produced in the lens.