title: The role of redox changes in oxygen sensing.
abstract: The specialized oxygen-sensing tissues include the carotid body and arterial smooth muscle cells in the pulmonary artery (PA) and ductus arteriosus (DA). We discuss the evidence that changes in oxygen tension are sensed through changes in redox status. "Redox" changes imply the giving or accepting of electrons. This might occur through the direct tunneling of electrons from mitochondria or redox couples to an effector protein (e.g. ion channel). Alternatively, the electron might be transferred through reactive oxygen species from mitochondria or an NADPH oxidase isoform. The PA's response to hypoxia and DA's response to normoxia result from reduction or oxidation, respectively. These opposing redox stimuli lead to K+ channel inhibition, membrane depolarization and an increase in cytosolic calcium and/or calcium sensitization that causes contraction. In the neuroendocrine cells (the type 1 cell of the carotid body, neuroepithelial body and adrenomedullary cells), the response is secretion. We examine the roles played by superoxide anion, hydrogen peroxide and the anti-oxidant enzymes in the signaling of oxygen tensions.
authors.affiliation: Department of Medicine, VA Medical Center and University of Minnesota, 1 Veteran's Drive, Minneapolis, MN 55417, USA. weirx002@umn.edu
authors.forename: E Kenneth
authors.initials: EK
authors.lastname: Weir
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Archer
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000378:metabolism; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D010100:Oxygen
references.citation: J Physiol. 2004 Apr 1;556(Pt 1):175-91
references.pmid: 14724184
references.citation: J Physiol. 1998 Oct 15;512 ( Pt 2):421-34
references.pmid: 9763632
references.citation: Circ Res. 2002 Jun 28;90(12):1307-15
references.pmid: 12089069
references.citation: Science. 2004 Dec 17;306(5704):2093-7
references.pmid: 15528406
references.citation: Proc Soc Exp Biol Med. 1999 Dec;222(3):222-35
references.pmid: 10601881
references.citation: J Appl Physiol (1985). 1989 Nov;67(5):1903-11
references.pmid: 2532193
references.citation: Biochem Biophys Res Commun. 1994 May 16;200(3):1586-91
references.pmid: 8185613
references.citation: Lancet. 1978 Mar 4;1(8062):476-7
references.pmid: 76024
references.citation: Adv Exp Med Biol. 2009;648:427-38
references.pmid: 19536508
references.citation: J Physiol. 1990 Sep;428:39-59
references.pmid: 2231419
references.citation: Am J Obstet Gynecol. 1992 Oct;167(4 Pt 1):946-9
references.pmid: 1415430
references.citation: Am J Respir Cell Mol Biol. 2006 Apr;34(4):505-13
references.pmid: 16357364
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13182-7
references.pmid: 8917565
references.citation: Circulation. 2004 Sep 14;110(11):1372-9
references.pmid: 15353504
references.citation: Circ Res. 1995 Jul;77(1):174-81
references.pmid: 7788875
references.citation: J Biol Chem. 1998 Oct 23;273(43):28510-5
references.pmid: 9774481
references.citation: Placenta. 2001 Apr;22(4):304-8
references.pmid: 11286565
references.citation: J Appl Physiol (1985). 2001 Apr;90(4):1299-306
references.pmid: 11247927
references.citation: Life Sci. 1980 Jun 9;26(23):1935-45
references.pmid: 6772902
references.citation: J Appl Physiol (1985). 1989 Nov;67(5):1912-21
references.pmid: 2532194
references.citation: Exp Physiol. 1995 Sep;80(5):825-34
references.pmid: 8546871
references.citation: Biochem Biophys Res Commun. 2002 Feb 22;291(2):332-7
references.pmid: 11846408
references.citation: J Biol Chem. 1981 Nov 10;256(21):10986-92
references.pmid: 7287745
references.citation: Prenat Diagn. 2009 Jul;29(7):691-6
references.pmid: 19399816
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Jan;282(1):L36-43
references.pmid: 11741813
references.citation: J Physiol. 2006 Aug 15;575(Pt 1):215-27
references.pmid: 16777942
references.citation: J Biol Chem. 2000 Mar 17;275(11):7684-92
references.pmid: 10713079
references.citation: Am J Hypertens. 2008 Oct;21(10):1152-6
references.pmid: 18670418
references.citation: PLoS One. 2009 Nov 26;4(11):e8045
references.pmid: 19956681
references.citation: Am J Physiol Cell Physiol. 2008 Apr;294(4):C945-56
references.pmid: 18234847
references.citation: Eur J Med Chem. 2008 Jun;43(6):1206-15
references.pmid: 17949858
references.citation: Exp Physiol. 2007 Sep;92(5):945-51
references.pmid: 17496002
references.citation: Am J Physiol. 1996 May;270(5 Pt 1):L803-9
references.pmid: 8967515
references.citation: J Physiol. 2001 May 15;533(Pt 1):253-61
references.pmid: 11351032
references.citation: Circ Res. 2002 Sep 20;91(6):478-86
references.pmid: 12242265
references.citation: Br J Pharmacol. 2004 Jan;141(1):105-13
references.pmid: 14656807
references.citation: Biochim Biophys Acta. 2004 Jun 7;1656(2-3):79-87
references.pmid: 15178469
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 Jan;290(1):L2-10
references.pmid: 16085672
references.citation: J Appl Physiol (1985). 1995 Jul;79(1):15-22
references.pmid: 7559213
references.citation: Eur Respir J. 2010 Aug;36(2):323-30
references.pmid: 20223914
references.citation: J Soc Gynecol Investig. 1996 Jul-Aug;3(4):179-84
references.pmid: 8796828
references.citation: Circ Res. 1968 May;22(5):573-88
references.pmid: 5648062
references.citation: Circ Res. 2010 Feb 19;106(3):526-35
references.pmid: 20019331
references.citation: Mol Cells. 2010 Jun;29(6):539-49
references.pmid: 20526816
references.citation: Circulation. 2006 Jun 6;113(22):2630-41
references.pmid: 16735674
references.citation: Eur Respir J. 2010 Aug;36(2):234-6
references.pmid: 20675778
references.citation: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H570-8
references.pmid: 18083891
references.citation: Pediatr Res. 2003 Jul;54(1):20-5
references.pmid: 12700368
references.citation: Neuroscience. 2007 Mar 2;145(1):130-41
references.pmid: 17207576
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R303-11
references.pmid: 19923358
references.citation: Free Radic Biol Med. 2007 Mar 1;42(5):642-53
references.pmid: 17291988
references.citation: J Appl Physiol (1985). 2006 Sep;101(3):995-8; discussion 998
references.pmid: 16902070
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Mar;292(3):L685-98
references.pmid: 17098807
references.citation: Respir Physiol. 1983 Sep;53(3):295-306
references.pmid: 6648060
references.citation: Clin Chem Lab Med. 2009;47(9):1073-80
references.pmid: 19728848
references.citation: Biochem J. 1975 Jan;146(1):53-65
references.pmid: 167718
references.citation: Herz. 1986 Jun;11(3):127-41
references.pmid: 3017827
references.citation: Circ Res. 1993 Dec;73(6):1100-12
references.pmid: 8222081
references.citation: Exp Physiol. 2008 Jan;93(1):133-8
references.pmid: 17993507
references.citation: Am J Physiol Cell Physiol. 2005 Feb;288(2):C366-76
references.pmid: 15469953
references.citation: Antioxid Redox Signal. 2010 Mar 1;12(5):595-602
references.pmid: 19747064
references.citation: FASEB J. 1995 Feb;9(2):183-9
references.pmid: 7781921
references.citation: Proc Soc Exp Biol Med. 1983 May;173(1):96-103
references.pmid: 6574522
references.citation: Circulation. 2007 Apr 3;115(13):1777-88
references.pmid: 17353442
references.citation: Am J Physiol Cell Physiol. 2003 Dec;285(6):C1377-85
references.pmid: 12890649
references.citation: Zhonghua Jie He He Hu Xi Za Zhi. 2002 Jan;25(1):33-5
references.pmid: 11953097
references.citation: Circ Res. 2006 Oct 27;99(9):970-8
references.pmid: 17008601
references.citation: J Physiol. 2003 May 1;548(Pt 3):789-800
references.pmid: 12626666
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Jan;286(1):L15-22
references.pmid: 12842809
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7944-9
references.pmid: 10393927
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Sep;295(3):L422-30
references.pmid: 18599502
references.citation: J Appl Physiol (1985). 2001 Jun;90(6):2249-56
references.pmid: 11356790
references.citation: Circulation. 2010 Jun 22;121(24):2661-71
references.pmid: 20529999
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):897-906
references.pmid: 20122895
references.citation: J Appl Physiol (1985). 1989 Jan;66(1):167-70
references.pmid: 2537281
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1984 Apr;56(4):900-5
references.pmid: 6427146
references.citation: J Physiol. 2001 Oct 1;536(Pt 1):211-24
references.pmid: 11579170
references.citation: Am J Physiol Cell Physiol. 2006 Mar;290(3):C907-16
references.pmid: 16236819
references.citation: Am J Respir Cell Mol Biol. 1995 Jan;12(1):41-9
references.pmid: 7529030
references.citation: Cardiovasc Res. 1999 Oct;44(1):215-22
references.pmid: 10615405
references.citation: J Appl Physiol (1985). 2006 Sep;101(3):993-5; discussion 999
references.pmid: 16675614
references.citation: Am J Physiol Heart Circ Physiol. 2009 Oct;297(4):H1453-61
references.pmid: 19666846
references.citation: Free Radic Biol Med. 2010 Feb 1;48(3):421-9
references.pmid: 19932748
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Oct;293(4):L952-9
references.pmid: 17693484
references.citation: Arch Biochem Biophys. 1982 Jul;216(2):477-84
references.pmid: 6287935
references.citation: N Engl J Med. 2005 Nov 10;353(19):2042-55
references.pmid: 16282179
references.citation: Pediatr Res. 2008 Feb;63(2):176-81
references.pmid: 18091358
references.citation: Chest. 1985 Oct;88(4 Suppl):249S-252S
references.pmid: 3840072
references.citation: J Physiol. 1996 Mar 1;491 ( Pt 2):511-8
references.pmid: 8866874
references.citation: Can J Physiol Pharmacol. 1977 Apr;55(2):251-7
references.pmid: 871957
references.citation: Cardiovasc Res. 2009 Mar 1;81(4):678-85
references.pmid: 19091790