Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin.
Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin.
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DOI：
10.1016/s0021-9258(17)41787-x
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发表时间：
1994-02
期刊：
影响因子：
--
通讯作者：
M. Goldberg;T. J. Schneider
中科院分区：
文献类型：
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作者：
M. Goldberg;T. J. Schneider
成功地适应相对低氧时期的能力对所有高等生命形式的生存至关重要。先前已鉴定出几个基因在低氧时上调；这些基因包括编码促红细胞生成素(EPO)、血小板衍生生长因子B链、内皮素、白细胞介素1α、鸟氨酸脱羧酶和血管内皮生长因子(VEGF)的基因。然而，感知缺氧的分子机制仍然是个谜。此外，尚不清楚上述基因是否共享共同的氧气感应信号转导途径。在这份报告中，我们展示了氧感应机制调节血管内皮生长因子和促红细胞生成素表达的许多相似之处。缺氧和氯化钴(CoCl2)显著上调这两种mRNAs的表达，放线菌亚胺显著延长这两种mRNAs的半衰期。此外，低氧诱导的EPO和血管内皮生长因子都被一氧化碳抑制。作为对这些基因低氧和钴诱导的信号转导途径研究的一部分，我们发现Jun和Fos原癌基因家族成员在暴露于这两种刺激的早期也上调了表达。这些发现支持这样一种假设，即在分子水平上感知缺氧的机制(S)可能是高度保守和严格调控的。
The ability to adapt successfully to periods of relative hypoxia is crucial to the survival of all higher life forms. Several genes have previously been identified which are up-regulated in response to hypoxia; these include the genes encoding erythropoietin (Epo), platelet-derived growth factor B chain, endothelin, interleukin-1 alpha, ornithine decarboxylase, and vascular endothelial growth factor (VEGF). However, the molecular mechanisms by which hypoxia is sensed remain enigmatic. In addition, it is unknown whether the genes mentioned share a common oxygen-sensing signal transduction pathway. In this report we demonstrate multiple similarities between the oxygen-sensing mechanisms regulating the expression of VEGF and Epo. The expression of both mRNAs is significantly up-regulated by hypoxia and cobalt chloride (CoCl2), and the half-life of both mRNAs is markedly prolonged by cycloheximide. In addition, hypoxic induction of both Epo and VEGF is inhibited by carbon monoxide. As part of our investigation into the signal transduction pathway responsible for the hypoxia and cobalt induction of these genes, we discovered that the expression of members of the jun and fos protooncogene families is also up-regulated early after exposure to either of these stimuli. These findings provide support for the hypothesis that the mechanism(s) by which hypoxia is sensed at a molecular level may be highly conserved and tightly regulated.