NADPH氧化酶和过氧化氢敏感的K+通道可能在气道化学感受器和小细胞肺癌细胞系中起氧传感器复合物的作用
NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines
肺神经上皮细胞(NEB)广泛分布于人和动物肺的气道粘膜。通过观察NEB细胞具有一种候选的氧传感器酶复合物(NADPH氧化酶)和一种氧敏K+电流，我们认为NEB可能具有气道化学感受器的功能。我们报道了过氧化氢敏感电压门控钾通道亚基(KH2O2) KV3.3a和NADPH氧化酶膜组分(gp91phox和p22phox)的mrna在胎兔和新生儿肺NEB细胞中共同表达。使用微荧光法和双氢或荷达明123作为探针来评估H2O2的生成，NEB细胞在基础条件下表现出氧化酶活性。内细胞显著刺激的氧化酶接触佛波醇(0.1μM),以斯帖被diphenyliodonium(5μM)。采用全细胞电压钳的研究表明，培养的胎兔NEB细胞K+电流表现出与Xenopus卵母细胞模型中KV3.3a转录本相似的失活特性。在常氧条件下，NEB细胞暴露于过氧化氢(过氧化氢是氧化酶分解的副产物)，导致K+向外电流增加，表明H2O2可能是调节o2敏感性K+通道的递质。
在小细胞肺癌细胞系中发现NADPH氧化酶膜细胞色素b的表达mRNA或应答蛋白产物，以及编码KV3.3a的mRNA。本研究为氧化酶-O2敏感的钾离子通道分子复合物在NEB细胞中作为O2传感器发挥作用提供了强有力的证据，该复合物在气道和NEB相关肿瘤中起化学感受器的作用。这种复合物可能代表了一种进化保守的生物化学链接，这种生物化学链接是一种膜结合的o2 -信号机制，被认为适用于其他细胞和生命形式。
关键词:肺神经上皮细胞，氧传感，活性氧中间体，非同位素原位杂交NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines
Pulmonary neuroepithelial bodies (NEB) are widely distributed throughout the airway mucosa of human and animal lungs. Based on the observation that NEB cells have a candidate oxygen sensor enzyme complex (NADPH oxidase) and an oxygen-sensitive K+ current, it has been suggested that NEB may function as airway chemoreceptors.
Here we report that mRNAs for both the hydrogen peroxide sensitive voltage gated potassium channel subunit (KH2O2) KV3.3a and membrane components of NADPH oxidase (gp91phox and p22phox) are coexpressed in the NEB cells of fetal rabbit and neonatal human lungs. Using a microfluorometry and dihydrorhodamine 123 as a probe to assess H2O2 generation, NEB cells exhibited oxidase activity under basal conditions. The oxidase in NEB cells was significantly stimulated by exposure to phorbol esther (0.1 μM) and inhibited by diphenyliodonium (5 μM).
Studies using whole-cell voltage clamp showed that the K+ current of cultured fetal rabbit NEB cells exhibited inactivating properties similar to KV3.3a transcripts expressed in Xenopus oocyte model. Exposure of NEB cells to hydrogen peroxide (H2O2, the dismuted by-product of the oxidase) under normoxia resulted in an increase of the outward K+ current indicating that H2O2 could be the transmitter modulating the O2-sensitive K+ channel. Expressed mRNAs or responding protein products for the NADPH oxidase membrane cytochrome b as well as mRNA encoding KV3.3a were identified in small cell lung carcinoma cell lines. The studies presented here provide strong evidence for an oxidase-O2 sensitive potassium channel molecular complex operating as an O2 sensor in NEB cells, which function as chemoreceptors in airways and in NEB related tumors. Such a complex may represent an evolutionary conserved biochemical link for a membrane bound O2-signaling mechanism proposed for other cells and life forms. Keywords: pulmonary neuroepithelial bodies, oxygen sensing, reactive oxygen intermediates, nonisotopic in situ hybridization
NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor... - Europe PMC Article - Europe PMC
http://europepmc.org/articles/PMC24067/
