Advertisement

Function of NADPH Oxidase and Signaling by Reactive Oxygen Species in Rat Carotid Body Type I Cells

  • L. HE
  • B. DINGER
  • C. GONZALEZ
  • A. OBESO
  • S. FIDONE
Part of the ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY book series (AEMB, volume 580)

Abstract

O2-sensing in the carotid body occurs in neuroectoderm-derived type I glomus cells, where hypoxia elicits a complex chemotransduction cascade involving membrane depolarization, Ca2+ entry and the release of excitatory neurotransmitters. Efforts to understand the exquisite O2-sensitivity of these cells have focused primarily on the relationship between PO2 and the activity of K+-channels. An important hypothesis developed by Acker and his colleagues suggests that coupling between local PO2 and the open-closed state of K+- channels is mediated by reactive oxygen species (ROS) generated by a phagocytic-like multisubunit enzyme, NADPH oxidase (Nox)(1). According to this scheme, ROS production will occur in proportion to the prevailing PO2, and a subset of K+-channels which control the EM, should close as ROS levels decrease. In O2-sensitive cells contained in lung neuroepithelial bodies (NEB), experiments have confirmed that ROS levels decrease in hypoxia, and that EM and K+-channel activity are indeed controlled by ROS produced by an Nox isoform similar, if not identical to the enzyme expressed in phagocytic cells that use ROS as part of an extracellular killing mechanism activated in response to invading micro-organisms(8; 15).

Keywords

Reactive Oxygen Species Production NADPH Oxidase Carotid Body Glomus Cell Benzenesulfonyl Fluoride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Acker H, Bolling B, Delpiano MA, Dafau E, Gorlach A and Holtermann G. The meaning of H2O2 generation in carotid body cells for PO2 chemoreception. J Auton Nerv Syst 41(1–2): 41–51, 1992.PubMedCrossRefGoogle Scholar
  2. 2.
    Babior BM. NADPH oxidase: An update. Blood 93(5): 1464–1476, 1999.PubMedGoogle Scholar
  3. 3.
    Brar SS, Kennedy TP, Sturrock AB, Huecksteadt TP, Quinn MT, Murphy TM, Chitano P and Hoidal JR. NADPH oxidase promotes NF-KB activation and proliferation in human airway smooth muscle. Am J Physiol Lung Cell Molec Physiol 282: L782–L795, 2002.Google Scholar
  4. 4.
    Buckler KJ. Background leak K+-currents and oxygen sensing in carotid body type 1 cells. Resp Physiol 115: 179–187, 1999.CrossRefGoogle Scholar
  5. 5.
    Buerk DG, Nair PK and Whalen WJ. Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body. J Appl Physiol 67: 1578–1584, 1989.PubMedGoogle Scholar
  6. 6.
    Cross AR, Henderson L, Jones OTG, Delpiano MA, Hentschel J and Acker H. Involvement of an NAD(P)H oxidase as a PO2 sensor protein in the rat carotid body. Biochem J 272: 743–747, 1990.PubMedGoogle Scholar
  7. 7.
    Diatchuk V, Lotan O, Koshkin V, Wikstroem P and Pick E. Inhibition of NADPH oxidase activation by 4-(2-aminoethyl)-benzenesulfonyl fluoride and related compounds. J Biol Chem 272(2): 13292–13301, 1997.PubMedCrossRefGoogle Scholar
  8. 8.
    Fu XW, Wang D, Nurse CA, Dinauer MC and Cutz E. NADPH oxidase is an O2 sensor in airway chemoreceptors: Evidence from K+ current modulation in wild-type and oxidasedeficient mice. PNAS 97(8): 4374–4379, 2000.PubMedCrossRefGoogle Scholar
  9. 9.
    He L, Dinger B, Sanders K, Hoidal J, Obeso A, Stensaas L, Fidone S and Gonzalez C. Effect of p47phox gene-deletion on reactive oxygen species (ROS) production and oxygen sensing in mouse carotid body chemoreceptor cells. Am J Phsiol in press: 2005.Google Scholar
  10. 10.
    He L, Chen J, Dinger B, Sanders K, Sundar K, Hoidal J and Fidone S. Characteristics of carotid body chemosensitivity in NADPH oxidase-deficient mice. Am J Physiol Cell Physiol 282: C27–C33, 2002.PubMedGoogle Scholar
  11. 11.
    Kummer W and Acker H. Immunohistochemical demonstration of four subunits of neutrophil NAD(P)H oxidase in type I cells of carotid body. J Appl Physiol 78(5): 1904–1909, 1995.PubMedGoogle Scholar
  12. 12.
    Lambeth JD. Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases. Current Opinion in Hematology 9: 11–17, 2002.PubMedCrossRefGoogle Scholar
  13. 13.
    Li J-M and Shah AJ. Intracellular localization and preassembly of the NADPH oxidase complex in cultured endothelial cells. J Biol Chem 277(22): 19952–19960, 2002.PubMedCrossRefGoogle Scholar
  14. 14.
    Lopez-Lopez JR and Gonzalez C. Time course of K+ current inhibition by low oxygen in chemoreceptor cells of adult rabbit carotid body: effects of carbon monoxide. FEBS Lett 299: 251–254, 1992.PubMedCrossRefGoogle Scholar
  15. 15.
    O'Kelly I, Lewis A, Peers C and Kemp PJ. O2 sensing by airway chemoreceptor-derived cells: Protein kinase C activation reveals functional evidence for involvement of NADPH oxidase. J Biol Chem 275(11): 7684–7692, 2000.PubMedCrossRefGoogle Scholar
  16. 16.
    Obeso A, Gomez-Nino A and Gonzalez C. NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and rabbit CB chemoreceptor cells. Am J Physiol 276(Cell Physiol.45): C593–C601, 1999.PubMedGoogle Scholar
  17. 17.
    Obeso A, Gonzalez C, Rigual R, Dinger B and Fidone S. Effect of low O2 on glucose uptake in rabbit carotid body. J Appl Physiol 74(5): 2387–2393, 1993.PubMedGoogle Scholar
  18. 18.
    Peers C and Kemp PJ. Acute oxygen sensing: Diverse but convergent mechanisms in airway and arterial chemoreceptors. Respir Res 2: 145–149, 2001.PubMedCrossRefGoogle Scholar
  19. 19.
    Porwol T, Ehleben W, Brand V and Acker H. Tissue oxygen sensor function of NADPH oxidase isoforms, and an unusual cytochrome aa3; producing reactive oxygen species. Resp Physiol 128: 331–348, 2001.CrossRefGoogle Scholar
  20. 20.
    Riesco-Fagundo AM, Pérez-García MT, Gonzalez C and López-López JR. O2 modulates large-conductance Ca2+-dependent K+ channels of rat chemoreceptor cells by a membranerestricted and CO-sensitive mechanism. Circ Res 89: 430–436, 2001.PubMedGoogle Scholar
  21. 21.
    Szöcs K, Lassè B, Sorescu D, Hilenski LL, Valppu L, Couse TL, Wilcox JN, Quinn MT, Lambeth JD and Griendling KK. Upregulation of Nox-Based NAD(P)H oxidases in restenosis after carotid injury. Arterioscler Thromb Vasc Biol 22: 21–27, 2002.PubMedCrossRefGoogle Scholar
  22. 22.
    Tarpey MM and Fridovich I. Methods of detection of vascular reactive species: Nitroc oxide, superoxide, hydrogen peroxide and peroxynitrite. Circ Res 89: 224–236, 2001.PubMedGoogle Scholar
  23. 23.
    Wyatt CN and Peers C. Ca2+-activated K+ channels in isolated type I cells of the neonatal rat carotid body. J Physiol 483.3: 559–565, 1995.Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  • L. HE
    • 1
  • B. DINGER
    • 1
  • C. GONZALEZ
    • 2
  • A. OBESO
    • 2
  • S. FIDONE
    • 1
  1. 1.Department of PhysiologyUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Departamento de Bioquimica y Biologia Molecular y Fisiologia/IBGMFacultad de Medicina. Universidad de Valladolid/CSIC.Valladolid.Spain

Personalised recommendations