Thioredoxin-related mechanisms in hyperoxic lung injury in mice
Thioredoxin-related mechanisms in hyperoxic lung injury in mice
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DOI：
10.1165/rcmb.2006-0376oc
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发表时间：
2007-10-01
影响因子：
6.4
通讯作者：
Smith, Charles V.
中科院分区：
文献类型：
--
作者：
Tipple, Trent E.;Welty, Stephen E.;Smith, Charles V.
谷胱甘肽还原酶（GR）将谷胱甘肽二硫化物（GSSG）还原为谷胱甘肽（GSH）可增强GSH依赖性抗氧化活性的效率。然而，GR缺陷（a1 Neu）小鼠对连续暴露于> 95%O-2（96 h：6.9 +/- 0.1 g右肺/kg体vs室内空气3.6 +/- 0.3）的急性肺损伤的敏感性低于C3 H/HeN对照小鼠（10.6 +/- 1.3 vs 4.2 +/- 0.3，P < 0.001）。a1 Neu小鼠的肝脏硫氧还蛋白（Trx）1和Trx 2水平高于C3 H/HeN小鼠，表明GR缺失的补偿。a1 Neu小鼠暴露于高氧96小时后，肺中的炎性浸润水平低于类似暴露的C3 H/HeN小鼠。硫氧还蛋白还原酶（TrxR）抑制剂金硫葡萄糖（ATG）预处理可加重高氧对a1 Neu小鼠肺损伤的影响（11.6 +/- 0.8，P< 0.001），但可减轻C3 H/HeN小鼠高氧肺水肿和炎症（6.3 +/- 0.4，P < 0.001）。ATG预处理后，肺GSH含量或肝GSH或GSSG水平无一致性变化。这些数据表明，调制的Trx/TrxR系统可能提供治疗上有用的改变细胞的抗氧化应激。ATG对高氧肺损伤的保护作用可能被证明是特别有用的治疗。
Reduction of glutathione disulfide (GSSG) to glutathione (GSH) by glutathione reductase (GR) enhances the efficiency of GSH-dependent antioxidant activities. However, GR-deficient (a1 Neu) mice are less susceptible to acute lung injury from continuous exposure to > 95% O-2 (96 h: 6.9 +/- 0.1 g right lung/kg body versus room air 3.6 +/- 0.3) than are C3H/HeN control mice (10.6 +/- 1.3 versus 4.2 +/- 0.3, P < 0.001). a1 Neu mice have greater hepatic thioredoxin (Trx)1 and Trx2 levels than do C3H/HeN mice, suggesting compensation for the absence of GR. a1 Neu mice exposed to hyperoxia for 96 hours showed lower levels of inflammatory infiltrates in lungs than did similarly exposed C3H/HeN mice. Pretreatment with aurothioglucose (ATG), a thioredoxin reductase (TrxR) inhibitor, exacerbated the effects of hyperoxia on lung injury in a1 Neu mice (11.6 +/- 0.8, P< 0.001), but attenuated hyperoxic lung edema and inflammation in C3H/HeN mice (6.3 +/- 0.4, P < 0.001). No consistent alterations were observed in lung GSH contents or liver GSH or GSSG levels after ATG pretreatment. The data suggest that modulation of Trx/TrxR systems might provide therapeutically useful alterations of cellular resistance to oxidant stresses. The protective effects of ATG against hyperoxic lung injury could prove to be particularly useful therapeutically.