缺氧诱导因子 1（HIF-1）诱导肺动脉平滑肌细胞电压门控钾（Kv）通道表达。
Hypoxia induces voltage-gated K+ (Kv) channel expression in pulmonary arterial smooth muscle cells through hypoxia-inducible factor-1 (HIF-1).
机构信息
Ion Channelopathy Research Center, Institute of Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
出版信息
Bosn J Basic Med Sci. 2012 Aug;12(3):158-63. doi: 10.17305/bjbms.2012.2463.
Hypoxia-inducible factor-1 (HIF-1) regulates the expression of hypoxia-inducible genes by binding erythropoietin (EPO) enhancer fragments. Of these genes, HIF-1 upregulates voltage-gated K+1.2 channels (Kv1.2) in rat PC12 cells. Whether HIF-1 regulates hypoxia-induced Kv channel expression in cultured pulmonary artery smooth muscle cells (PASMCs), however, has not been determined. In this study, we investigated the effects of hypoxia on the expression of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in PASMCs and examined the direct role of HIF-1 by transfecting either wild type or mutant EPO enhancer fragments. Our results showed that 18 h exposure to hypoxia significantly increased the expression of Kv1.2, Kv1.5, Kv2.1, and Kv9.3; and this hypoxia-induced upregulation was completely inhibited after transfection with the wild type but not mutant EPO enhancer fragment. These results indicate that HIF-1 regulates hypoxia-stimulated induction of Kv1.2 Kv1.5, Kv2.1, and Kv9.3 channels in cultured PASMCs.
缺氧诱导因子-1（HIF-1）通过结合促红细胞生成素（EPO）增强子片段来调节缺氧诱导基因的表达。在这些基因中，HIF-1 在大鼠 PC12 细胞中上调电压门控 K+1.2 通道（Kv1.2）。然而，HIF-1 是否调节培养的肺动脉平滑肌细胞（PASMC）中缺氧诱导的 Kv 通道表达尚未确定。在这项研究中，我们研究了缺氧对 PASMC 中 Kv1.2 Kv1.5、Kv2.1 和 Kv9.3 通道表达的影响，并通过转染野生型或突变型 EPO 增强子片段来检查 HIF-1 的直接作用。我们的结果表明，18 小时缺氧暴露显著增加了 Kv1.2、Kv1.5、Kv2.1 和 Kv9.3 的表达；并且这种缺氧诱导的上调在转染野生型但不是突变型 EPO 增强子片段后完全被抑制。这些结果表明，HIF-1 调节培养的 PASMC 中 Kv1.2 Kv1.5、Kv2.1 和 Kv9.3 通道的缺氧刺激诱导。
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