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Enzyme-Linked Acute Oxygen Sensing in Airway and Arterial Chemoreceptors – Invited Article

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Arterial Chemoreceptors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 648))

Abstract

Researchers have speculated as to the molecular basis of O2 sensing for decades. In more recent years, since the discovery of ion channels as identified effectors for O2 sensing pathways, research has focussed on possible pathways coupling a reduction in hypoxia to altered ion channel activity. The most extensively studied systems are the K+ channels which are inhibited by hypoxia in chemoreceptor tissues (carotid and neuroepithelial bodies). In this review, we consider the evidence supporting the involvement of well defined enzymes in mediating the regulation of K+ channels by hypoxia. Specifically, we focus on the roles proposed for three enzyme systems; NADPH oxidase, heme oxygenase and AMP activated protein kinase. These systems differ in that the former two utilise O2 directly (to form superoxide in the case of NADPH oxidase, and as a co-factor in the degradation of heme to carbon monoxide, bilirubin and ferrous iron in the case of heme oxygenase), but the third responds to shifts in the AMP:ATP ratio, so responds to changes in O2 levels more indirectly. We consider the evidence in favour of each of these systems, and highlight their differential importance in different systems and species. Whilst the evidence for each playing an important role in different tissues is strong, there is a clear need for further study, and current awareness indicates that no one specific cell type may rely on a single mechanism for O2 sensing.

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References

  • Aley, P. K., Porter, K. E., Boyle, J. P., Kemp, P. J., & Peers, C. (2005). Hypoxic modulation of Ca2+z signaling in human venous endothelial cells. Multiple roles for reactive oxygen species. J Biol. Chem., 280, 13349–13354.

    Article  PubMed  CAS  Google Scholar 

  • Cross, A. R., Herderson, L., Jones, O. T. G., Delpiano, M. A., Hentschel, J., & Acker, H. (1990). Involvement of an NAD(P)H oxidase as a pO2 sensor protein in the rat carotid body. Biochem. J., 272, 743–747.

    PubMed  CAS  Google Scholar 

  • Evans, A. M., Mustard, K. J., Wyatt, C. N., Peers, C., Dipp, M., Kumar, P., Kinnear, N. P., & Hardie, D. G. (2005). Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells? J Biol. Chem., 280, 41504–41511.

    Article  PubMed  CAS  Google Scholar 

  • Fandrey, J., Gorr, T. A., & Gassmann, M. (2006). Regulating cellular oxygen sensing by hydroxylation. Cardiovasc. Res., 71, 642–651.

    Article  PubMed  CAS  Google Scholar 

  • Fu, X. W., Wang, D., Nurse, C. A., Dinauer, M. C., & Cutz, E. (2000). NADPH oxidase is an O2 sensor in airway chemoreceptors: evidence from K+ current modulation in wild type and oxidase-deficient mice. Proc. Natl. Acad. Sci. USA, 97, 4374–4379.

    Article  PubMed  CAS  Google Scholar 

  • Hardie, D. G., Hawley, S. A., & Scott, J. W. (2006). AMP-activated protein kinase–development of the energy sensor concept. J. Physiol., 574, 7–15.

    Article  PubMed  CAS  Google Scholar 

  • He, L., Dinger, B., Sanders, K., Hoidal, J., Obeso, A., Stensaas, L., Fidone, S., & Gonzalez, C. (2005). Effect of p47phox gene deletion on ROS production and oxygen sensing in mouse carotid body chemoreceptor cells. Am. J. Physiol. Lung Cell. Mol. Physiol., 289, L916–L924.

    Article  PubMed  CAS  Google Scholar 

  • Hou, S., Xu, R., Heinemann, S. H., & Hoshi, T. (2008). The RCK1 high-affinity Ca2+ sensor confers carbon monoxide sensitivity to Slo1 BK channels. Proc. Natl. Acad. Sci. USA, 105, 4039–4043.

    Article  PubMed  CAS  Google Scholar 

  • Jaggar, J. H., Li, A., Parfenova, H., Liu, J., Umstot, E. S., Dopico, A. M., & Leffler, C. W. (2005). Heme is a carbon monoxide receptor for large-conductance Ca2+-activated K+ channels. Circ. Res., 97, 805–812.

    Article  PubMed  CAS  Google Scholar 

  • Kemp, P. J. (2005). Hemeoxygenase-2 as an O2 sensor in K+ channel-dependent chemotransduction. Biochem. Biophys. Res. Commun., 338, 648–652.

    Article  PubMed  CAS  Google Scholar 

  • Lambeth, J. D., Kawahara, T., & Diebold, B. (2007). Regulation of Nox and Duox enzymatic activity and expression. Free Radic. Biol. Med., 43, 319–331.

    Article  PubMed  CAS  Google Scholar 

  • Lewis, A., Peers, C., Ashford, M. L. J., & Kemp, P. J. (2002). Hypoxia inhibits human recombinant maxi K+ channels by a mechanism which is membrane delimited and Ca2+-sensitive. J. Physiol., 540, 771–780.

    Article  PubMed  CAS  Google Scholar 

  • Maines, M. D. & Gibbs, P. E. (2005). 30 some years of heme oxygenase: from a “molecular wrecking ball” to a “mesmerizing” trigger of cellular events. Biochem. Biophys. Res. Commun., 338, 568–577.

    Article  PubMed  CAS  Google Scholar 

  • O’Kelly, I., Lewis, A., Peers, C., & Kemp, P. J. (2000). O2 sensing by airway chemoreceptor-derived cells: protein kinase C activation reveals functional evidence for involvement of NADPH oxidase. J. Biol. Chem., 275, 7684–7692.

    Article  PubMed  Google Scholar 

  • O’Kelly, I., Peers, C., & Kemp, P. J. (2001). NADPH oxidase does not account fully for O2 sensing in model airway chemoreceptor cells. Biochem. Biophys. Res. Comm., 283, 1131–1134.

    Article  PubMed  Google Scholar 

  • Ortega-Saenz, P., Pascual, A., Gomez-Diaz, R., & Lopez-Barneo, J. (2006). Acute oxygen sensing in heme oxygenase-2 null mice. J. Gen. Physiol., 128, 405–411.

    Article  PubMed  CAS  Google Scholar 

  • Peers, C. (1990). Hypoxic suppression of K+ currents in type-I carotid-body cells – selective effect on the Ca2-activated K+ current. Neurosci. Lett., 119, 253–256.

    Article  PubMed  CAS  Google Scholar 

  • Perez-Garcia, M. T., Colinas, O., Miguel-Velado, E., Moreno-Dominguez, A., & Lopez-Lopez, J. R. (2004). Characterization of the Kv channels of mouse carotid body chemoreceptor cells and their role in oxygen sensing. J. Physiol., 557, 457–471.

    Article  PubMed  CAS  Google Scholar 

  • Prabhakar, N. R., Dinerman, J. L., Agani, F. H., & Snyder, S. H. (1995). Carbon monoxide: a role in carotid body chemoreception. Proc. Natl. Acac. Sci. USA, 92, 1994–1997.

    Article  CAS  Google Scholar 

  • Riesco-Fagundo, A. M., Perez-Garcia, M. T., Gonzalez, C., & Lopez-Lopez, J. R. (2001). O2 modulates large-conductance Ca2+-dependent K+ channels of rat chemoreceptor cells by a membrane-restricted and CO-sensitive mechanism. Circ. Res., 89, 430–436.

    Article  PubMed  CAS  Google Scholar 

  • Roy, A., Rozanov, C., Mokashi, A., Daudu, P., Al-mehdi, A. B., Shams, H., & Lahiri, S. (2000). Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell [Ca2+]i and respiratory responses to hypoxia. Brain Res., 872, 188–193.

    Article  PubMed  CAS  Google Scholar 

  • Ryter, S. W., Alam, J., & Choi, A. M. (2006). Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev., 86, 583–650.

    Article  PubMed  CAS  Google Scholar 

  • Tang, X. D., Xu, R., Reynolds, M. F., Garcia, M. L., Heinemann, S. H., & Hoshi, T. (2003). Haem can bind to and inhibit mammalian calcium-dependent Slo1 BK channels. Nature, 425, 531–535.

    Article  PubMed  CAS  Google Scholar 

  • Wang, D., Youngson, C., Wong, V., Yeger, H., Dinauer, M. C., Vega-Saenz de Miera, E., Rudy, B., & Cutz, E. (1996). NADPH-oxidase and hydrogen peroxide sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines. Proc. Natl. Acad. Sci. USA, 93, 13182–13187.

    Article  PubMed  CAS  Google Scholar 

  • Ward, J. P. (2008). Oxygen sensors in context. Biochim. Biophys. Acta, 1777, 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Williams, S. E., Brazier, S. P., Baban, N., Telezhkin, V., Muller, C. T., Riccardi, D., & Kemp, P. J. (2008). A structural motif in the C-terminal tail of slo1 confers carbon monoxide sensitivity to human BKCa channels. Pflugers Arch., 456, 561–572.

    Article  PubMed  CAS  Google Scholar 

  • Williams, S. E., Wootton, P., Mason, H. S., Bould, J., Iles, D. E., Riccardi, D., Peers, C., & Kemp, P. J. (2004). Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel. Science, 306, 2093–2097.

    Article  PubMed  CAS  Google Scholar 

  • Wyatt, C. N., Mustard, K. J., Pearson, S. A., Dallas, M. L., Atkinson, L., Kumar, P., Peers, C., Hardie, D. G., & Evans, A. M. (2007). AMP-activated protein kinase mediates carotid body excitation by hypoxia. J Biol. Chem., 282, 8092–8098.

    Article  PubMed  CAS  Google Scholar 

  • Yamaguchi, S., Balbir, A., Schofield, B., Coram, J., Tankersley, C. G., Fitzgerald, R. S., O’Donnell, C. P., & Shirahata, M. (2003). Structural and functional differences of the carotid body between DBA/2 J and A/J strains of mice. J. Appl. Physiol., 94, 1536–1542.

    PubMed  Google Scholar 

  • Youngson, C., Nurse, C., Yeger, H., & Cutz, E. (1993). Oxygen sensing in airway chemoreceptors. Nature, 365, 153–155.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to J. Paul Kemp .

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Kemp, J.P., Peers, C. (2009). Enzyme-Linked Acute Oxygen Sensing in Airway and Arterial Chemoreceptors – Invited Article . 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_4

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