Padgaonkar Vanita A, Leverenz Victor R, Bhat Aparna V, Pelliccia Sara E, Giblin Frank J
Eye Research Institute, Oakland University, Rochester, MI.
Photochem Photobiol. 2015 Mar-Apr;91(2):387-96. doi: 10.1111/php.12404. Epub 2015 Jan 8.
This study compares the abilities of the glutathione (GSH) and thioredoxin (Trx) antioxidant systems in defending cultured 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 thioredoxin reductase (TrxR). Two levels of O2 , 3% and 20%, were employed during a 1 h exposure of the cells to 25 J cm(-2) of UVA radiation (338-400 nm wavelength, peak at 365 nm). Inhibition of TrxR activity by CDNB, combined with exposure to UVA light, produced a substantial loss of LECs and cell damage, with the effects being considerably more severe at 20% O2 compared to 3%. In contrast, depletion of GSH by BSO, combined with exposure to UVA light, produced only 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 presented a challenge for the lens epithelium, it was well tolerated under normal conditions. The results demonstrate an important role for TrxR activity in defending the lens epithelium against UVA light, possibly related to the ability of the Trx system to assist DNA synthesis following UVA-induced cell damage.
本研究比较了谷胱甘肽(GSH)和硫氧还蛋白(Trx)抗氧化系统在保护培养的人晶状体上皮细胞(LECs)免受紫外线A(UVA)照射方面的能力。用L-丁硫氨酸-(S,R)-亚砜亚胺(BSO)或1-氯-2,4-二硝基苯(CDNB)消耗GSH水平。CDNB处理还抑制了硫氧还蛋白还原酶(TrxR)的活性。在细胞暴露于25 J cm⁻²的UVA辐射(波长338 - 400 nm,峰值在365 nm)1小时期间,采用了3%和20%两个氧气水平。CDNB对TrxR活性的抑制与UVA照射相结合,导致LECs大量损失和细胞损伤,在20%氧气条件下的影响比3%时严重得多。相比之下,BSO对GSH的消耗与UVA照射相结合,仅导致轻微的细胞损失,没有明显的形态学影响。过氧化氢酶对UVA诱导的失活高度敏感,但对保护作用并非必需。尽管UVA对晶状体上皮构成了挑战,但在正常条件下它具有良好的耐受性。结果表明TrxR活性在保护晶状体上皮免受UVA照射方面起着重要作用,这可能与Trx系统在UVA诱导的细胞损伤后协助DNA合成的能力有关。