Subacute Mild Hypoxia Increases Histamine-stimulated Calcium Oscillation Frequency in Pulmonary Artery Endothelial Cells
Subacute Mild Hypoxia Increases Histamine-stimulated Calcium Oscillation Frequency in Pulmonary Artery Endothelial Cells
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亚急性轻度缺氧增加肺动脉内皮细胞中组胺刺激的钙振荡频率
DOI：
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发表时间：
2005-06
影响因子：
0.3
通讯作者：
Hu Qing-Hua
中科院分区：
文献类型：
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作者：
Jin Si;Chen Jian-Guo;Zhu Li-Ping;Liu Sheng-Yuan;Wang Di-Xun;Hu Qing-Hua
在激动剂刺激下，钙振荡可能以频率解码的方式调控基因转录，从而提供细胞内转录水平的指标。为探讨持续低氧是否可使细胞对组胺反应敏感或减弱，在肺动脉内皮细胞（PAECs）中观察了亚急性轻度低氧24 h对组胺刺激的钙振荡频率的影响。结果表明：（1）亚急性轻度缺氧24 h可显著增加PAECs内组胺刺激的钙振荡频率。低氧后PAECs钙振荡的平均频率显著高于常氧时。(2)NADPH氧化酶抑制剂，diphenylene iodonium chloride（DPI，10μmol/L）消除了组胺刺激的常氧和缺氧后肺动脉内皮细胞钙振荡; c. (3)黄嘌呤氧化酶抑制剂oxypurinol（100μmol/L）对PAECs钙振荡频率无明显影响。然而，它显著降低了缺氧后PAECs钙振荡频率的升高。这些结果表明，在与持续缺氧相关的肺部疾病期间，PAEC对组胺变得更敏感。在组胺刺激过程中，NADPH氧化酶在产生钙振荡中起关键作用，而黄嘌呤氧化酶可能至少部分地促进缺氧后PAECs钙振荡频率的增加。
Calcium oscillation may regulate gene transcription in a frequency-decoding manner during agonist stimulation, which provides an indicator of transcription level in cells. To determine whether persistent exposure to hypoxia may sensitize or blunt cell response to histamine, the effects of 24 h subacute mild hypoxia on histamine-stimulated calcium oscillation frequency were examined in pulmonary artery endothelial cells (PAECs). The results are: (1) 24 h subacute mild hypoxia significantly increased the histamine-stimulated calcium oscillation frequency in PAECs. The averaged frequency of calcium oscillation in posthypoxic PAECs was significantly higher than that in normoxic ones. (2) NADPH oxidase inhibitor, diphenylene iodonium chloride (DPI, 10μmol/L), abolished histamine-stimulated calcium oscillations both in normoxic and posthypoxic PAECs. (3) Xanthine oxidase inhibitor, oxypurinol (100μmol/L), did not affect the calcium oscillation frequency in normoxic PAECs. However, it significantly decreased the elevation of calcium oscillation frequency in posthypoxic PAECs. These results demonstrated that, during pulmonary disease related to persistent hypoxia, PAECs become more sensitive to histamine. During histamine stimulation, NADPH oxidase plays a critical role in generating calcium oscillations, while xanthine oxidase may contribute to, at least in part, the increase of calcium oscillation frequency in posthypoxic PAECs.