Nitric oxide-inducible expression of heme oxygenase-1 in human cells - Translation-independent stabilization of the mRNA and evidence for direct action of nitric oxide
Nitric oxide-inducible expression of heme oxygenase-1 in human cells - Translation-independent stabilization of the mRNA and evidence for direct action of nitric oxide
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DOI：
10.1074/jbc.275.42.32688
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发表时间：
2000-10-20
影响因子：
4.8
通讯作者：
Demple, B
中科院分区：
文献类型：
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作者：
Bouton, C;Demple, B
哺乳动物细胞中血红素加氧酶-1 (HO-1) 的表达有助于抵抗各种类型的自由基损伤。一氧化氮 (NO) 在许多细胞类型中诱导 HO-1，但转录或转录后效应对这种诱导的具体贡献仍未解决。在这里，我们表明 IMR-90 和 HeLa 细胞中 HO-1 mRNA 表达的程度取决于 NO 递送速率，并且 HeLa 中的诱导发生速度比人成纤维细胞 (IMR-90) 细胞慢。我们使用了一种特定的 NO 清除剂（2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1 1-氧基 3-氧化物），它完全阻止了 NO 诱导的 HO-1 表达，表明 NO 在这种诱导中具有直接信号传导作用。通过在 NO 暴露期间抑制转录，我们证实 NO 处理激活了一种稳定 HO-1 mRNA 的机制。IMR-90 细胞中 HO-1 mRNA 半衰期的增加与 NO 释放速率的增加直接相关。我们还表明 HO-1 信息的稳定不需要从头合成蛋白质。总的来说，这些结果表明 HO-1 mRNA 的稳定性可以根据 NO 暴露进行微调，并且对人成纤维细胞的影响是由预先存在的蛋白质介导的。
Expression of heme oxygenase-l (HO-1) in mammalian cells contributes to resistance to various types of free radical damage. Nitric oxide (NO) induces HO-1 in many cell types, but the specific contribution of transcriptional or post-transcriptional effects to this induction have remained unresolved. Here we show that the extent of HO-1 mRNA expression in IMR-90 and HeLa cells depends on the rate of NO delivery, and that the induction occurs more slowly in HeLa than in human fibroblast (IMR-90) cells. We used a specific NO scavenger (2-(4-carboxylphenyl)-4,4,5,5-tetramethylimidazolin-1 1-oxyl 3-oxide) that completely prevented the inducible expression of HO-1 by NO, pointing to direct signaling action of NO in this induction. By inhibiting transcription during the NO exposure, we have confirmed that NO treatment activates a mechanism that stabilizes HO-1 mRNA The increase in the HO-1 mRNA half-life in IMR-90 cells was directly correlated with increasing rates of NO release. We also show here that the stabilization of the HO-1 message does not require de novo protein synthesis. Collectively, these results show that stabilization of HO-1 mRNA can be finely tuned to the NO exposure, and that the effect in human fibroblasts is mediated by a pre-existing protein.