Hass M A, Iqbal J, Clerch L B, Frank L, Massaro D
Calvin and Flavia Oak Asthma Research and Treatment Facility, University of Miami School of Medicine, Florida 33136.
J Clin Invest. 1989 Apr;83(4):1241-6. doi: 10.1172/JCI114007.
The synthesis of Cu,Zn SOD by rat lung increases spontaneously in the fetus in late gestation and during exposure of neonatal and adult rats to greater than 95% O2. To explore the regulation of these increases, we measured rat lung Cu,Zn SOD synthesis and activity. We also cloned and sequenced a rat lung Cu,Zn SOD cDNA that was used to measure Cu,Zn SOD mRNA concentration. We found that (a) under normal gestational and postgestational conditions the synthesis of this enzyme was regulated pretranslationally; (b) the increased synthesis that occurs under hyperoxia (greater than 95% O2), was pretranslationally mediated in otherwise unmanipulated neonatal rats but translationally controlled in hyperoxic adult rats; and (c) in lungs of rats made tolerant to greater than 95% O2 by allowing 24 h rest in air after an initial 48 h in greater than 95% O2, the increased Cu,Zn SOD synthesis that occurred during the second period of hyperoxia was regulated pretranslationally. We conclude Cu,Zn SOD gene expression in the lung is developmentally regulated under normal conditions and in response to an oxidant challenge. Tolerance, whether endogenous or induced, appears to require the accumulation of increased amounts of Cu,Zn SOD mRNA.
大鼠肺中铜锌超氧化物歧化酶（Cu,Zn SOD）的合成在妊娠后期的胎儿以及新生和成年大鼠暴露于大于95%氧气的情况下会自发增加。为了探究这些增加的调节机制，我们测量了大鼠肺中Cu,Zn SOD的合成和活性。我们还克隆并测序了大鼠肺Cu,Zn SOD cDNA，用于测量Cu,Zn SOD mRNA浓度。我们发现：（a）在正常妊娠和产后条件下，该酶的合成在翻译前受到调节；（b）在高氧（大于95%氧气）条件下发生的合成增加，在未进行其他操作的新生大鼠中是由翻译前介导的，但在高氧成年大鼠中是由翻译控制的；（c）在最初48小时暴露于大于95%氧气后，在空气中休息24小时从而对大于95%氧气产生耐受的大鼠肺中，在第二个高氧期发生的Cu,Zn SOD合成增加是由翻译前调节的。我们得出结论，肺中Cu,Zn SOD基因表达在正常条件下以及对氧化应激的反应中受到发育调节。耐受性，无论是内源性的还是诱导性的，似乎都需要积累增加量的Cu,Zn SOD mRNA。
