Abstract
Abstract In pulmonary neuroepithelial bodies (NEB), presumed airway chemoreceptors, classical NADPH oxidase (gp91 phox, NOX2) is co-expressed with O2 sensitive K+ channels (K+O2) and functions as an O2 sensor. Here we examined related NADPH oxidase homologues “novel oxidases “(NOX 1, 3&4) and their possible involvement in O2 sensing. For immunolocalization we used specific antibodies against various NADPH components and K+ (O2) subunits to label NEB in rat /rabbit lung and NEB related H146 tumor cell line. For gene expression profiling of NEB cells microdissected from human lung, and H146 cells, we used custom MultiGene-12TM RT-PCR array that included NADPH oxidase components and homologues /accessory proteins (NOX1-4, phox-p22, p40, p47, p67, Rac1, NOXO1 and NOXA1) and K+O2 channels (Kv -1.2, 1.5, 2.1, 3.1, 3.3, 3.4, 4.2, 4.3;TASK1-3). In rat lung, NOX2, NOX4, p22phox, Kv3.3 (and Kv3.4 in rabbit) and TASK1 localized to the apical plasma membrane of NEB cells, and membrane or sub-membrane regions in H146 cells. NEB and H146 cells expressed all NOX proteins except NOX3, as well as all K+O2 channels, except Kv1.5 and Kv4.3. Co-immunoprecipitation using Western blot multicolor Quantum dot labeling showed NOX2 molecular complexes with Kv but not with TASK, while NOX4 associated with TASK1 but not with Kv channel proteins. Hypoxia -induced serotonin release was inhibited in H 146 cells by siRNA to NOX2, while siRNA to NOX4 had only a partial effect, implicating NOX 2 as the predominant NEB cell O2 sensor. Present findings support NEB cell specific plasma membrane model of O2 sensing, and suggest unique NOX/K+O2 channel combinations for diverse physiological NEB functions.
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Cutz, E., Pan, J., Yeger, H. (2009). The Role of NOX2 and “Novel Oxidases” in Airway Chemoreceptor O2 Sensing. In: Gonzalez, C., Nurse, C.A., Peers, C. (eds) Arterial Chemoreceptors. Advances in Experimental Medicine and Biology, vol 648. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2259-2_49
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DOI: https://doi.org/10.1007/978-90-481-2259-2_49
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