Thioredoxin Reductase Activity may be More Important than GSH Level in Protecting Human Lens Epithelial Cells against UVA Light

ABSTRACT This study compares the abilities of the glutathione (GSH)and thioredoxin (Trx) antioxidant systems in defending cul-tured human lens epithelial cells (LECs) against UVA light.Levels of GSH were depleted with either L-buthionine-(S,R)-sulfoximine (BSO) or 1-chloro-2,4-dinitrobenzene (CDNB).CDNB treatment also inhibited the activity of thioredoxinreductase (TrxR). Two levels of O 2 , 3% and 20%, wereemployed during a 1 h exposure of the cells to 25 J cm 2 ofUVA radiation (338–400 nm wavelength, peak at 365 nm).Inhibition of TrxR activity by CDNB, combined with expo-sure to UVA light, produced a substantial loss of LECs andcell damage, with the effects being considerably more severeat 20% O 2 compared to 3%. In contrast, depletion of GSHby BSO, combined with exposure to UVA light, producedonly a slight cell loss, with no apparent morphological effects.Catalase was highly sensitive to UVA-induced inactivation,but was not essential for protection. Although UVA light pre-sented a challenge for the lens epithelium, it was well toler-ated under normal conditions. The results demonstrate animportant role for TrxR activity in defending the lens epithe-lium against UVA light, possibly related to the ability of theTrx system to assist DNA synthesis following UVA-inducedcell damage.