Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
25 Mar 2022
25 Mar 2022
Historique:
entrez:
25
3
2022
pubmed:
26
3
2022
medline:
26
3
2022
Statut:
ppublish
Résumé
As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.
Identifiants
pubmed: 35333571
doi: 10.1126/sciadv.abm1444
pmc: PMC8956269
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabm1444Références
Sci Signal. 2020 Jan 21;13(615):
pubmed: 31848220
J Appl Physiol. 1975 Jan;38(1):143-6
pubmed: 1110230
Br J Pharmacol. 2008 Apr;153(8):1697-705
pubmed: 18297105
Proc Jpn Acad Ser B Phys Biol Sci. 2017;93(7):464-482
pubmed: 28769017
Mediators Inflamm. 2008;2008:106507
pubmed: 19096513
Nat Chem Biol. 2011 Aug 28;7(10):701-11
pubmed: 21873995
J Neurosci. 2015 Jul 22;35(29):10460-73
pubmed: 26203141
J Physiol. 2001 Feb 15;531(Pt 1):165-70
pubmed: 11179400
Am J Physiol. 1990 Nov;259(5 Pt 2):R911-20
pubmed: 2240275
Pharmacol Ther. 2013 May;138(2):272-84
pubmed: 23356979
Br J Pharmacol. 2008 Mar;153(6):1324-30
pubmed: 18204483
J Physiol. 2018 Aug;596(15):3043-3065
pubmed: 29742297
J Neurosci. 2007 Jan 3;27(1):141-51
pubmed: 17202481
J Physiol. 2018 Aug;596(15):2969-2976
pubmed: 29214644
Am J Physiol. 1951 Jul;166(1):45-54
pubmed: 14857147
Neurosci Lett. 2007 Mar 19;415(1):73-6
pubmed: 17254709
J Appl Physiol (1985). 2000 May;88(5):1840-52
pubmed: 10797149
Brain Res Bull. 1982 Mar;8(3):267-72
pubmed: 7093734
Am J Blood Res. 2019 Feb 15;9(1):1-14
pubmed: 30899601
Sci Rep. 2016 Nov 22;6:37460
pubmed: 27874100
J Cereb Blood Flow Metab. 1998 Jan;18(1):75-87
pubmed: 9428308
Annu Rev Physiol. 2020 Feb 10;82:127-149
pubmed: 31618601
Channels (Austin). 2017 Nov 2;11(6):624-635
pubmed: 28876976
Biophys J. 2010 Jul 21;99(2):407-16
pubmed: 20643058
Rev Physiol Biochem Pharmacol. 1988;110:147-285
pubmed: 3285441
J Appl Physiol (1985). 2012 Jan;112(1):212-24
pubmed: 21903882
J Physiol. 2012 Oct 1;590(19):4933-44
pubmed: 22777672
Sci Rep. 2017 Sep 12;7(1):11280
pubmed: 28900295
J Physiol. 1909 Dec 23;39(5):346-53
pubmed: 16992986
J Biol Chem. 2004 Apr 30;279(18):18323-33
pubmed: 14966111
Front Physiol. 2021 Mar 25;12:645904
pubmed: 33841182
J Appl Physiol (1985). 2009 Sep;107(3):662-9
pubmed: 19520839
Am J Physiol. 1981 Nov;241(5):H679-83
pubmed: 7304756
J Neurophysiol. 2015 Aug;114(2):989-98
pubmed: 26108952
Exp Physiol. 2016 Dec 1;101(12):1451-1462
pubmed: 27519960
Mol Pain. 2007 Dec 17;3:40
pubmed: 18086313
Compr Physiol. 2012 Jan;2(1):141-219
pubmed: 23728973
J Appl Physiol (1985). 1990 Jan;68(1):53-8
pubmed: 2107169
Am J Physiol Regul Integr Comp Physiol. 2001 Aug;281(2):R528-38
pubmed: 11448857
Recept Channels. 2001;7(6):429-39
pubmed: 11918346
Histochem Cell Biol. 1995 May;103(5):379-85
pubmed: 7641070
J Physiol. 2009 Feb 15;587(Pt 4):883-96
pubmed: 19103684
Biochemistry. 1993 Aug 24;32(33):8512-7
pubmed: 7689333
J Appl Physiol (1985). 2004 Jan;96(1):367-74
pubmed: 14660498
Nature. 2008 Dec 11;456(7223):745-9
pubmed: 18971930
Am J Physiol Renal Physiol. 2016 Jul 1;311(1):F1-F11
pubmed: 27147669
J Physiol. 2019 Jul;597(13):3407-3423
pubmed: 31077360
Front Physiol. 2018 Mar 06;9:163
pubmed: 29559921
Prog Neurobiol. 1994 Oct;44(2):197-219
pubmed: 7831477
J Comp Neurol. 2009 Jun 10;514(5):492-506
pubmed: 19350665
Free Radic Biol Med. 2014 Nov;76:208-26
pubmed: 25157786
J Biol Chem. 1999 Sep 3;274(36):25218-26
pubmed: 10464242
Neuroscience. 2003;121(3):641-7
pubmed: 14568024
Eur J Biochem. 1990 Apr 20;189(1):155-66
pubmed: 2158889
J Neurophysiol. 2000 Nov;84(5):2572-81
pubmed: 11067999
Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1571-80
pubmed: 15677524
Thromb Haemost. 2009 Apr;101(4):619-25
pubmed: 19350103
Neurosci Lett. 1993 Jul 23;157(2):219-22
pubmed: 7694196
Compr Physiol. 2016 Mar 15;6(2):1005-41
pubmed: 27065173
J Neurosci Methods. 2002 Apr 30;116(1):77-87
pubmed: 12007985
J Appl Physiol (1985). 2016 Oct 1;121(4):944-952
pubmed: 27609199
Stroke. 1986 Nov-Dec;17(6):1183-9
pubmed: 3810718
Nat Commun. 2014;5:3284
pubmed: 24518663
J Physiol. 2018 Aug;596(15):2977-2983
pubmed: 29359806
Respir Physiol. 1997 Nov;110(2-3):219-28
pubmed: 9407614
Circ Res. 1977 Jul;41(1):128-34
pubmed: 862136
Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d
pubmed: 21890489
J Physiol. 1910 Dec 31;41(5):416-49
pubmed: 16993035
J Physiol. 2018 Aug;596(15):3149-3169
pubmed: 29159869
J Enzyme Inhib Med Chem. 2013 Feb;28(1):95-104
pubmed: 22136506
Biochem J. 2016 Sep 1;473(17):2561-72
pubmed: 27574022
Neuroscience. 2014 Jun 6;269:67-78
pubmed: 24680940
Curr Biol. 2020 Sep 7;30(17):3378-3396.e7
pubmed: 32679097
J Physiol. 2018 Aug;596(15):3245-3269
pubmed: 28678385
Adv Exp Med Biol. 2015;860:227-32
pubmed: 26303485
Compr Physiol. 2014 Oct;4(4):1511-62
pubmed: 25428853
Am J Physiol Renal Physiol. 2009 Feb;296(2):F266-76
pubmed: 19091787
J Appl Physiol (1985). 2017 Nov 1;123(5):1344-1349
pubmed: 28522760
J Biol Chem. 1998 Jan 9;273(2):945-9
pubmed: 9422754
Biochem J. 1990 Dec 15;272(3):743-7
pubmed: 2268299
Eur J Neurosci. 2008 Mar;27(5):1131-42
pubmed: 18364033
J Physiol. 2002 Oct 15;544(2):511-20
pubmed: 12381823
Science. 2010 Jul 30;329(5991):571-5
pubmed: 20647426
Epilepsy Res. 2007 May;74(2-3):155-62
pubmed: 17434291