Clerch L B, Massaro D
Lung Biology Laboratory, Georgetown University School of Medicine, Washington, District of Columbia 20007.
J Clin Invest. 1993 Feb;91(2):499-508. doi: 10.1172/JCI116228.
Tolerance to hyperoxia usually requires an increase of lung antioxidant enzyme (AOE) activity. We used rats with different degrees of tolerance to > 95% O2 to evaluate the importance of individual AOEs for tolerance; we also explored the regulation of AOE gene expression. During exposure of adult rats to > 95% O2, lung manganese superoxide dismutase (MnSOD) activity fell approximately 50% despite a threefold increase of MnSOD mRNA concentration; addition of a reducing agent to lung extracts from O2-exposed rats partially restored MnSOD activity. Endotoxin induced tolerance to O2 (a) without elevating Cu,Zn superoxide dismutase activity, (b) with increases of catalase and glutathione peroxidase (GP) activity of the same magnitude as occurred in O2-saline rats, but (c) with MnSOD activity 1.5-1.9-fold higher than in air-saline rats and 1.4-3.6-fold higher than in O2-saline rats. Endotoxin elevated the concentration of MnSOD and GP mRNAs without increasing their stability. O2 elevated MnSOD mRNA concentration, and increased its stability. O2 plus endotoxin increased the concentration and stability of MnSOD, catalase, and GP mRNAs. These data suggest that in adult rats tolerance to hyperoxia requires increased MnSOD activity; the data show gene expression and regulation vary among the AOEs, and that increased stability of the AOEs' mRNAs plays an important role in AOE gene expression and in tolerance to hyperoxia.
对高氧的耐受性通常需要肺抗氧化酶（AOE）活性增加。我们使用对>95%氧气具有不同程度耐受性的大鼠来评估个体AOE对耐受性的重要性；我们还探究了AOE基因表达的调控。在成年大鼠暴露于>95%氧气的过程中，肺锰超氧化物歧化酶（MnSOD）活性下降了约50%，尽管MnSOD mRNA浓度增加了三倍；向暴露于氧气的大鼠的肺提取物中添加还原剂可部分恢复MnSOD活性。内毒素诱导对氧气的耐受性：（a）不提高铜锌超氧化物歧化酶活性，（b）过氧化氢酶和谷胱甘肽过氧化物酶（GP）活性的增加幅度与暴露于氧气的生理盐水处理大鼠相同，但（c）MnSOD活性比空气生理盐水处理大鼠高1.5 - 1.9倍，比氧气生理盐水处理大鼠高1.4 - 3.6倍。内毒素提高了MnSOD和GP mRNA的浓度，但没有增加它们的稳定性。氧气提高了MnSOD mRNA的浓度，并增加了其稳定性。氧气加内毒素增加了MnSOD、过氧化氢酶和GP mRNA的浓度及稳定性。这些数据表明，在成年大鼠中，对高氧的耐受性需要增加MnSOD活性；数据显示AOE之间的基因表达和调控各不相同，且AOE mRNA稳定性的增加在AOE基因表达和对高氧的耐受性中起重要作用。
