Induction of thioredoxin and thioredoxin reductase gene expression in lungs of newborn primates by oxygen
Induction of thioredoxin and thioredoxin reductase gene expression in lungs of newborn primates by oxygen
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DOI：
10.1152/ajplung.1999.276.3.l530
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发表时间：
1999-03-01
影响因子：
4.9
通讯作者：
White, CW
中科院分区：
文献类型：
--
作者：
Das, KC;Guo, XL;White, CW
硫氧还蛋白 (TRX) 是一种有效的蛋白质二硫键氧化还原酶，在抗氧化防御以及细胞生长和信号转导过程（其中包括一氧化氮的产生）的调节中发挥重要作用。我们报告说，肺 TRX 及其还原酶 TR 在出生时被 O-2 特异性上调。在整个妊娠晚期，狒狒胎儿肺中 TRX 和 TR 的 mRNA 持续低水平表达。然而。早产后（妊娠 185 天中的 125 天或 140 天），肺 TRX 和 TR mRNA 随着 O-2 或空气呼吸的开始而迅速增加。呼吸空气的足月新生儿肺部的肺 TRX mRNA 也有所增加。呼吸 100% O-2 的早产动物（140 天）会在 7-14 天内出现慢性肺病。这些动物在出生 1、6 或 10 天后比胎儿对照动物具有更高的 TRX 和 TR mRNA。在给予较低 O-2 浓度（根据需要）且未发展为慢性肺部疾病的 140 天动物中，肺 TRX 和 TR mRNA 在第 1 天和第 6 天也增加，但在第 10 天不显着。在胎儿远端肺外植体培养中，相对于 1% O-2，TRX 和 TR mRNA 在 4 小时内在 95% O-2 中升高，并且在不同妊娠期的反应相似。相比之下，早产动物（125或140天）的肺外植体中的TRX蛋白没有增加，但在暴露于高氧后的近足月（175天）胎儿狒狒的肺外植体中TRX蛋白却增加了。然而，肺 TRX 蛋白和活性以及 TR 活性最终在体内因高氧（6 天）而增加。在成年狒狒肺外植体中也观察到 TRX 和 TR mRNA 对 95% O-2 的反应有所增加。当确定 TRX 氧化还原状态时，增加的 O-2 张力将 TRX 转变为氧化形式。用放线菌素 D 处理肺外植体可抑制 95% O-2 中的 TRX 和 TR mRNA 增加，表明 O-2 的转录调节作用。 TRX 和 TR 基因表达对 O-2 的反应急剧增加，表明这些蛋白质在从相对无氧的胎儿生命到出生时 O-2 呼吸的过渡过程中发挥着重要作用。
Thioredoxin (TRX) is a potent protein disulfide oxidoreductase important in antioxidant defense and regulation of cell growth and signal transduction processes, among them the production of nitric oxide. We report that lung TRX and its reductase, TR, are specifically upregulated at birth by O-2. Throughout the third trimester, mRNAs for TRX and TR were expressed constitutively at low levels in fetal baboon lungs. However. after premature birth (125 or 140 of 185 days gestation), lung TRX and TR mRNAs increased rapidly with the onset of O-2 or air breathing. Lung TRX mRNA also increased in lungs of term newborns with air breathing. Premature animals (140 days) breathing 100% O-2 develop chronic lung disease within 7-14 days. These animals had greater TRX and TR mRNAs after 1, 6, or 10 days of life than fetal control animals. In 140-day animals given lesser O-2 concentrations (as needed) who do not develop chronic lung disease, lung TRX and TR mRNAs were also increased on days 1 and 6 but not significantly on day 10. In fetal distal lung explant culture, mRNAs for TRX and TR were elevated within 4 h in 95% O-2 relative to 1% O-2, and the response was similar at various gestations. In contrast, TRX protein did not increase in lung explants from premature animals (125 or 140 days) but did in those from near-term (175-day) fetal baboons after exposure to hyperoxia. However, lung TRX protein and activity, as well as TR activity, eventually did increase in vivo in response to hyperoxia (6 days). Increases in TRX and TR mRNAs in response to 95% O-2 also were observed in adult baboon lung explants. When TRX redox status was determined, increased O-2 tension shifted TRX to its oxidized form. Treatment of lung explants with actinomycin D inhibited TRX and TR mRNA increases in 95% O-2, indicating transcriptional regulation by O-2. The acute increase in gene expression for both TRX and TR in response to O-2 suggests an important role for these proteins during the transition from relatively anaerobic fetal life to O-2 breathing at birth.