Hypoxia Increases ROS Signaling and Cytosolic Ca2+ in Pulmonary Artery Smooth Muscle Cells of Mouse Lungs Slices
Hypoxia Increases ROS Signaling and Cytosolic Ca2+ in Pulmonary Artery Smooth Muscle Cells of Mouse Lungs Slices
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DOI：
10.1089/ars.2009.2862
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发表时间：
2010-03-01
影响因子：
6.6
通讯作者：
Schumacker, Paul T.
中科院分区：
文献类型：
--
作者：
Desireddi, Jennifer R.;Farrow, Kathryn N.;Schumacker, Paul T.
在肺泡缺氧时，毛细血管前动脉收缩，这种反应称为缺氧性肺血管收缩(HPV)。肺动脉平滑肌细胞(PASMCs)检测Po-2减少并触发收缩的机制尚不完全清楚。以往对培养的PASMCs的研究表明，低氧可诱导PASMCs产生更多的活性氧(ROS)，但这些结果可能不能反映PASMCs在其自然组织环境中的反应。因此，我们评估了低氧诱导表达氧化还原敏感蛋白RoGFP的精密切割小鼠肺切片PASMCs胞浆ROS的变化。肺切片与低氧介质(1.5%O-2)灌流可导致RoGFP从常氧基础上显著氧化，而胞浆过氧化氢酶的过度表达可减弱这种氧化作用。低氧灌流也使[Ca~(2+)](I)高于常氧基线；胞浆过氧化氢酶过度表达或给予合成的超氧化物歧化酶-过氧化氢酶模拟物EUK134可显著减弱这种反应。无细胞外钙时，缺氧引起的[Ca~(2+)](I)升高被取消，表明ROS信号触发细胞外钙内流。总之，这些结果表明，在急性HPV反应期间，细胞内ROS信号的增加是精密切割的小鼠肺切片中PASMCs[Ca~(2+)](I)增加所必需的。抗氧化剂。氧化还原信号。12595-602。
Precapillary arteries constrict during alveolar hypoxia in a response known as hypoxic pulmonary vasoconstriction (HPV). The mechanism by which pulmonary arterial smooth muscle cells (PASMCs) detect a decrease in Po-2 and trigger contraction is not fully understood. Previous studies in cultured PASMCs show that hypoxia induces an increase in reactive oxygen species (ROS) production, but these results may not reflect responses of PASMCs in their native tissue environment. We therefore assessed hypoxia-induced changes in cytosolic ROS in PASMCs of precision-cut mouse lung slices expressing the redox-sensitive protein, RoGFP. Superfusion of lung slices with hypoxic media (1.5% O-2) resulted in a significant oxidation of RoGFP from normoxic baseline that was attenuated by overexpression of cytosolic catalase. Hypoxic superfusion also increased [Ca2+](i) above normoxic baseline; this response was significantly attenuated by cytosolic catalase overexpression or by the administration of EUK134, a synthetic SOD-catalase mimetic. The hypoxia-induced increase in [Ca2+](i) was abolished in the absence of extracellular Ca2+, indicating that ROS signals trigger entry of extracellular calcium. Collectively, these results indicate that an increase in cytosolic ROS signaling is required for the increase in [Ca2+](i) in PASMCs in precision-cut mouse lung slices during the acute HPV response. Antioxid. Redox Signal. 12, 595-602.