Mitochondria depletion abolishes agonist-induced Ca2+ plateau in airway smooth muscle cells: potential role of H2O2
Mitochondria depletion abolishes agonist-induced Ca2+ plateau in airway smooth muscle cells: potential role of H2O2
复制标题
线粒体耗竭消除了气道平滑肌细胞中激动剂诱导的 Ca2 平台：H2O2 的潜在作用。
DOI：
10.1152/ajplung.00134.2009
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发表时间：
2010-02-01
影响因子：
4.9
通讯作者：
Hu, Qinghua
中科院分区：
文献类型：
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作者：
Chen, Taoxiang;Zhu, Liping;Hu, Qinghua
线粒体作为一个独立的细胞器调节激动剂诱导的胞质 Ca(2+) 浓度反应的持续阶段的机制尚不清楚。通过暴露于溴化乙锭并提供丙酮酸和尿苷，我们建立了线粒体 DNA (mtDNA) 耗尽的大鼠气道平滑肌细胞 (RASMC)，并保持细胞能量。暴露于 2 µM 组胺后，对照 RASMC 中的 [Ca(2+)](i) 增加至峰值，然后稳定在基线以上，而 mtDNA 耗尽的 RASMC 中的 [Ca(2+)](i) 跃升至峰值，然后下降至基线，没有任何平台。 mtDNA 耗竭明显减弱了组胺诱导的细胞内活性氧的产生。通过同时暴露于 2 µM 组胺和 0.1 µM 外源 H(2)O(2)（其本身不影响 [Ca(2+)](i)），mtDNA 耗尽的 RASMC 中 [Ca(2+)](i) 动力学的上述差异被逆转。细胞内 H(2)O(2) 分解消除组胺诱导的 RASMC 中 [Ca(2+)](i) 持续升高。因此，线粒体通过 H(2)O(2) 依赖性机制调节激动剂诱导的持续 [Ca(2+)](i) 升高。
The mechanisms by which mitochondria regulate the sustained phase of agonist-induced responses in cytosolic Ca(2+) concentration as an independent organelle in whole is not clear. By exposing to ethidium bromide and supplying pyruvate and uridine, we established mitochondrial DNA (mtDNA)-depleted rat airway smooth muscle cells (RASMCs) with maintained cellular energy. Upon an exposure to 2 microM histamine, [Ca(2+)](i) in control RASMCs increased to a peak followed by a plateau above baseline, whereas [Ca(2+)](i) in mtDNA-depleted RASMCs jumped to a peak and then declined to baseline without any plateau. mtDNA depletion apparently attenuated intracellular reactive oxygen species generation induced by histamine. By coexposure to 2 microM histamine and 0.1 microM exogenous H(2)O(2), which did not affect [Ca(2+)](i) by itself, the above difference in [Ca(2+)](i) kinetics in mtDNA-depleted RASMCs was reversed. Intracellular H(2)O(2) decomposition abolishes histamine-induced sustained elevation in [Ca(2+)](i) in RASMCs. Thus, mitochondria regulate agonist-induced sustained [Ca(2+)](i) elevation by a H(2)O(2)-dependent mechanism.