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高氧暴露及恢复过程中肺内抗氧化酶表达的分子机制

Molecular mechanisms of antioxidant enzyme expression in lung during exposure to and recovery from hyperoxia.

作者信息

Clerch L B, Massaro D, Berkovich A

机构信息

Lung Biology Laboratory, Georgetown University School of Medicine, Washington, DC 20007-2197, USA.

出版信息

Am J Physiol. 1998 Mar;274(3):L313-9. doi: 10.1152/ajplung.1998.274.3.L313.

DOI:10.1152/ajplung.1998.274.3.L313
PMID:9530165
Abstract

Manganese superoxide dismutase (MnSOD) activity falls approximately 50% in lung during 48 h of exposure of adult rats to > 95% O2 (L. B. Clerch and D. Massaro. J. Clin. Invest. 91: 499-508, 1993). We now show that hyperoxia also decreased MnSOD activity in lungs of adult baboons, making the phenomenon potentially more important to humans. In rats, a decrease in lung MnSOD activity during an initial 48 h of exposure to > 95% O2 and its increase during an immediately subsequent 24 h in air were due to decreases and increases, respectively, in MnSOD specific activity and synthesis rate; the latter was due to altered translational efficiency. The concentration in the lung of copper-zinc superoxide dismutase mRNA, catalase mRNA, and glutathione peroxidase mRNA, unchanged during the initial 48 h of exposure to O2, rose approximately twofold during reexposure to O2 after 24 h in air. The demonstration that the fall in MnSOD activity is translationally and posttranslationally regulated during the initial exposure to hyperoxia suggests that gene transfer to increase MnSOD activity in hyperoxic lungs may also require therapy that maintains translational efficiency and MnSOD specific activity.

摘要

成年大鼠暴露于>95%氧气环境48小时后,肺中的锰超氧化物歧化酶(MnSOD)活性大约下降50%(L.B.克莱奇和D.马萨罗。《临床研究杂志》91:499 - 508,1993)。我们现在表明,高氧也会降低成年狒狒肺中的MnSOD活性,这使得该现象对人类可能更具重要性。在大鼠中,暴露于>95%氧气环境的最初48小时内肺中MnSOD活性下降,随后立即在空气中暴露24小时期间其活性增加,分别是由于MnSOD比活性和合成速率的下降和增加;后者是由于翻译效率改变。在暴露于氧气的最初48小时内,肺中铜锌超氧化物歧化酶mRNA、过氧化氢酶mRNA和谷胱甘肽过氧化物酶mRNA的浓度未发生变化,但在空气中暴露24小时后再次暴露于氧气期间,其浓度大约增加了两倍。在最初暴露于高氧环境期间,MnSOD活性的下降是由翻译和翻译后调控的,这表明在高氧肺中通过基因转移增加MnSOD活性可能还需要维持翻译效率和MnSOD比活性的治疗方法。

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