Loss of thioredoxin activity as an important contributor to oxidative stress in lens of diabetic rats

Abstract

Abstract Purpose Thioredoxin (Trx) is a redox regulator whose bioavailability in mammalian tissues is regulated by its intrinsic binding protein, thioredoxin‐binding protein‐2 (TBP‐2). The purpose of this study is to investigate whether diabetic condition can alter the ratio of Trx and TBP‐2 expressions in the lens that may contribute to cataract formation. Methods Streptozotocin (STZ at 75 mg/kg) induced diabetic rats were divided into aldose reductase inhibitor (0.0125% AL1576) treated and untreated groups. Rats without STZ injection were used as controls. Lenses from 3 and 8 wks post STZ injection were used to determine GSH level, Trx activity, and Western blot analysis for Trx and TBP‐2 protein levels. Results The lenses in the diabetic untreated group showed slight haziness in 3 wks, and moderate to severe opacity in 8 wks while all lenses in the ARI‐treated or control groups remained clear in both ages. The untreated diabetic group showed severe loss in GSH (< 20% of control in both 3 and 8 wks) and Trx activity (< 35% of the control in both 3 and 8 wks). TBP‐2 expression although was unchanged at 3 wks but elevated ~4‐fold over the control in 8 wks while Trx expression remained constant at both time points. ARI treatment protected the GSH level, Trx activity, and TBP‐2 expression in these lenses. Conclusion Diabetic condition induced TBP‐2 expression in the lens with concurrent suppression of Trx activity. The results suggest that the loss of the bioavailability of TRx, in conjunction with a severe GSH depletion, is likely to contribute to the oxidative stress observed in diabetic conditions. Furthermore the observation that ARI can normalize these changes suggests a role of osmotic stress in Trx/TBP‐2 imbalance.