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O2 Sensing by Airway Chemoreceptor-derived cells protein kinase C activation reveals functional evidence for involvement of NADPH oxidase

O'Kelly, Ita, Lewis, Anthony and Kemp, Paul J. 2000. O2 Sensing by Airway Chemoreceptor-derived cells protein kinase C activation reveals functional evidence for involvement of NADPH oxidase. Journal of Biological Chemistry 275 (11) , pp. 7684-7692. 10.1074/jbc.275.11.7684

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Abstract

Accumulating evidence suggests that neuroepithelial bodies are airway O2 sensors. Recently, we have established the H-146 small cell lung carcinoma line as a suitable model to study the biochemical basis of neuroepithelial body cell chemotransduction. Here we explore the possibility that hypoxic modulation of K+ channels is intimately linked to activity of NADPH oxidase. Graded hypoxia caused graded inhibition of whole cell K+ currents, which correlated well with membrane depolarization. Pretreatment with the phorbol ester, 12-O-tetradecanoyl (TPA), inhibited K+ currents at all potentials. Although 4α-phorbol 12,13-didecanoate and TPA in the presence of bisindolylmaleimide were also able to depress K+ currents, only TPA could significantly ameliorate hypoxic depression of these currents. Thus, protein kinase C (PKC) activation modulates the sensitivity of these cells to changes inpO2. Furthermore, because the addition of H2O2, a downstream product of NADPH oxidase, could only activate K+ currents during hypoxia (when endogenous H2O2 production is suppressed), it appears likely that PKC modulates the affinity of NADPH oxidase for O2 potentially via phosphorylation of the p47phox subunit, which is present in these cells. These data show that PKC is an important regulator of the O2-transduction pathway and suggests that NADPH oxidase represents a significant component of the airway O2sensor.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 0021-9258
Last Modified: 04 Jun 2017 06:40
URI: http://orca-mwe.cf.ac.uk/id/eprint/63425

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