RGD Reference Report - The role of NOX2 and "novel oxidases" in airway chemoreceptor O(2) sensing. - Rat Genome Database

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The role of NOX2 and "novel oxidases" in airway chemoreceptor O(2) sensing.

Authors: Cutz, E  Pan, J  Yeger, H 
Citation: Cutz E, etal., Adv Exp Med Biol. 2009;648:427-38.
RGD ID: 2317856
Pubmed: PMID:19536508   (View Abstract at PubMed)
DOI: DOI:10.1007/978-90-481-2259-2_49   (Journal Full-text)

In pulmonary neuroepithelial bodies (NEB), presumed airway chemoreceptors, classical NADPH oxidase (gp91 phox, NOX2) is co-expressed with O(2) sensitive K(+) channels (K(+)O(2)) and functions as an O(2) sensor. Here we examined related NADPH oxidase homologues "novel oxidases "(NOX 1, 3&4) and their possible involvement in O(2) sensing. For immunolocalization we used specific antibodies against various NADPH components and K(+) (O(2)) 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(+)O(2) 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(+)O(2) 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 O(2) sensor. Present findings support NEB cell specific plasma membrane model of O(2) sensing, and suggest unique NOX/K(+)O(2) channel combinations for diverse physiological NEB functions.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
apical plasma membrane  IDA 2317856; 2317856 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyba  (cytochrome b-245 alpha chain)
Nox4  (NADPH oxidase 4)


Additional Information