Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery
Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery
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DOI：
10.1007/s12576-010-0105-z
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发表时间：
2010-09-01
影响因子：
2.3
通讯作者：
Zhu, Daling
中科院分区：
文献类型：
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作者：
Guo, Lei;Qiu, Zhaoping;Zhu, Daling
我们以前报道过缺氧激活肺15-脂氧合酶(15-LOX)，该酶催化花生四烯酸产生15-HETE，导致新生兔肺动脉收缩。低氧抑制Kv2.1通道的表达。虽然低氧对Kv通道的抑制可能是通过15-HETE介导的，但直接证据仍然缺乏。为了探讨15-LOX/15-HETE通路是否参与低氧诱导的Kv2.1通道下调，我们利用15-LOX阻滞剂、半定量聚合酶链式反应和蛋白质印迹分析进行了研究。我们发现，在低氧条件下，阻断内源性15-HETE后，Kv2.1通道在肺动脉平滑肌细胞(PASMCs)和肺动脉(PA)的mRNA和蛋白水平均显著上调。与12-HETE和5-HETE相比，15-HETE进一步降低常氧条件下培养的PASMC和PA中Kv2.1通道的表达。这些数据表明，低氧通过内源性15-HETE抑制了PA中Kv2.1通道的表达。
We have previously reported that hypoxia activates lung 15-lipoxygenase (15-LOX), which catalyzes arachidonic acid to produce 15-HETE, leading to constriction of neonatal rabbit pulmonary arteries. Hypoxia suppresses Kv2.1 channel expression. Although the Kv channel inhibition by hypoxia is likely to be mediated through 15-HETE, direct evidence is still lacking. To explore whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of Kv2.1 channel, we performed studies using 15-LOX blockers, semi-quantitative PCR and western blot analysis. We found that Kv2.1 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery (PA) after blockade of endogenous 15-HETE under hypoxic condition. 15-HETE further decreased Kv2.1 channel expression in comparison with 12-HETE and 5-HETE in cultured PASMCs and PA under normoxic conditions. These data indicate that hypoxia suppresses Kv2.1 channel expression through endogenous 15-HETE in PA.