Abstract
A number of diseases and conditions have been associated with prolonged or persistent exposure to non-physiological levels of reactive oxygen species (ROS). Similarly, ROS underproduction due to loss-of-function mutations in superoxide or hydrogen peroxide (H2O2)-generating enzymes is a risk factor or causative for certain diseases. However, ROS are required for basic cell functions; in particular the diffusible second messenger H2O2 that serves as signaling molecule in redox processes. This activity sets H2O2 apart from highly reactive oxygen radicals and influences the approach to drug discovery, clinical utility, and therapeutic intervention. Here we review the chemical and biological fundamentals of ROS with emphasis on H2O2 as a signaling conduit and initiator of redox relays and propose an integrated view of physiological versus non-physiological reactive species. Therapeutic interventions that target persistently altered ROS levels should include both selective inhibition of a specific source of primary ROS and careful consideration of a targeted pro-oxidant approach, an avenue that is still underdeveloped. Both strategies require attention to redox dynamics in complex cellular systems, integration of the overall spatiotemporal cellular environment, and target validation to yield effective and safe therapeutics.
Graphical Abstract
The only professional primary ROS producers are NADPH oxidases (NOX1-5, DUOX1-2). Many other enzymes, e.g., xanthine oxidase (XO), monoamine oxidases (MAO), lysyl oxidases (LO), lipoxygenase (LOX), and cyclooxygenase (COX), produce superoxide and H2O2 secondary to their primary metabolic function. Superoxide is too reactive to disseminate, but H2O2 is diffusible, only limited by adjacent PRDXs or GPXs, and can be apically secreted and imported into cells through aquaporin (AQP) channels. H2O2 redox signaling includes oxidation of the active site thiol in protein tyrosine phosphatases, which will inhibit their activity and thereby increase tyrosine phosphorylation on target proteins. Essential functions include the oxidative burst by NOX2 as antimicrobial innate immune response; gastrointestinal NOX1 and DUOX2 generating low H2O2 concentrations sufficient to trigger antivirulence mechanisms; and thyroidal DUOX2 essential for providing H2O2 reduced by TPO to oxidize iodide to an iodinating form which is then attached to tyrosyls in TG. Loss-of-function (LoF) variants in TPO or DUOX2 cause congenital hypothyroidism and LoF variants in the NOX2 complex chronic granulomatous disease.
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References
Ahl D, Liu H, Schreiber O, Roos S, Phillipson M, Holm L (2016) Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice. Acta Physiol 217(4):300–310. https://doi.org/10.1111/apha.12695
Alvarez LA, Kovacic L, Rodriguez J, Gosemann JH, Kubica M, Pircalabioru GG, Friedmacher F, Cean A, Ghise A, Sarandan MB, Puri P, Daff S, Plettner E, von Kriegsheim A, Bourke B, Knaus UG (2016) NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA. Proc Natl Acad Sci U S A 113(37):10406–10411. https://doi.org/10.1073/pnas.1605443113
Ambruso DR, Ellison MA, Thurman GW, Leto TL (2012) Peroxiredoxin 6 translocates to the plasma membrane during neutrophil activation and is required for optimal NADPH oxidase activity. Biochim Biophys Acta 1823(2):306–315. https://doi.org/10.1016/j.bbamcr.2011.11.014
Atassi F, Servin AL (2010) Individual and co-operative roles of lactic acid and hydrogen peroxide in the killing activity of enteric strain Lactobacillus johnsonii NCC933 and vaginal strain Lactobacillus gasseri KS120.1 against enteric, uropathogenic and vaginosis-associated pathogens. FEMS Microbiol Lett 304(1):29–38. https://doi.org/10.1111/j.1574-6968.2009.01887.x
Augsburger F, Filippova A, Rasti D, Seredenina T, Lam M, Maghzal G, Mahiout Z, Jansen-Durr P, Knaus UG, Doroshow J, Stocker R, Krause KH, Jaquet V (2019) Pharmacological characterization of the seven human NOX isoforms and their inhibitors. Redox Biol 26:101272. https://doi.org/10.1016/j.redox.2019.101272
Aviello G, Knaus UG (2018) NADPH oxidases and ROS signaling in the gastrointestinal tract. Mucosal Immunol 11(4):1011–1023. https://doi.org/10.1038/s41385-018-0021-8
Aviello G, Singh AK, O’Neill S, Conroy E, Gallagher W, D’Agostino G, Walker AW, Bourke B, Scholz D, Knaus UG (2019) Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects. Mucosal Immunol 12(6):1316–1326. https://doi.org/10.1038/s41385-019-0205-x
Bayley R, Kite KA, McGettrick HM, Smith JP, Kitas GD, Buckley CD, Young SP (2015) The autoimmune-associated genetic variant PTPN22 R620W enhances neutrophil activation and function in patients with rheumatoid arthritis and healthy individuals. Ann Rheum Dis 74(8):1588–1595. https://doi.org/10.1136/annrheumdis-2013-204796
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313. 87/1/245 [pii]. https://doi.org/10.1152/physrev.00044.2005
Bilsborough J, Targan SR, Snapper SB (2016) Therapeutic targets in inflammatory bowel disease: current and future. Am J Gastroenterol Suppl 3(3):27–37. https://doi.org/10.1038/ajgsup.2016.18
Bogeski I, Niemeyer BA (2014) Redox regulation of ion channels. Antioxid Redox Signal 21(6):859–862. https://doi.org/10.1089/ars.2014.6019
Brigelius-Flohe R, Flohe L (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15(8):2335–2381. https://doi.org/10.1089/ars.2010.3534
Brigelius-Flohe R, Maiorino M (2013) Glutathione peroxidases. Biochim Biophys Acta 1830(5):3289–3303. https://doi.org/10.1016/j.bbagen.2012.11.020
Campbell EL, Bruyninckx WJ, Kelly CJ, Glover LE, McNamee EN, Bowers BE, Bayless AJ, Scully M, Saeedi BJ, Golden-Mason L, Ehrentraut SF, Curtis VF, Burgess A, Garvey JF, Sorensen A, Nemenoff R, Jedlicka P, Taylor CT, Kominsky DJ, Colgan SP (2014) Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation. Immunity 40(1):66–77. https://doi.org/10.1016/j.immuni.2013.11.020
Carre A, Louzada RA, Fortunato RS, Ameziane-El-Hassani R, Morand S, Ogryzko V, de Carvalho DP, Grasberger H, Leto TL, Dupuy C (2015) When an intramolecular disulfide bridge governs the interaction of DUOX2 with its partner DUOXA2. Antioxid Redox Signal 23(9):724–733. https://doi.org/10.1089/ars.2015.6265
Collins Y, Chouchani ET, James AM, Menger KE, Cocheme HM, Murphy MP (2012) Mitochondrial redox signalling at a glance. J Cell Sci 125(Pt 4):801–806. https://doi.org/10.1242/jcs.098475
Corcionivoschi N, Alvarez LA, Sharp TH, Strengert M, Alemka A, Mantell J, Verkade P, Knaus UG, Bourke B (2012) Mucosal reactive oxygen species decrease virulence by disrupting campylobacter jejuni phosphotyrosine signaling. Cell Host Microbe 12(1):47–59. https://doi.org/10.1016/j.chom.2012.05.018
Cross AR, Segal AW (2004) The NADPH oxidase of professional phagocytes--prototype of the NOX electron transport chain systems. Biochim Biophys Acta 1657(1):1–22. https://doi.org/10.1016/j.bbabio.2004.03.008. S0005272804000556 [pii]
De Deken X, Miot F (2019) DUOX defects and their roles in congenital hypothyroidism. Methods Mol Biol 1982:667–693. https://doi.org/10.1007/978-1-4939-9424-3_37
De Ravin SS, Li L, Wu X, Choi U, Allen C, Koontz S, Lee J, Theobald-Whiting N, Chu J, Garofalo M, Sweeney C, Kardava L, Moir S, Viley A, Natarajan P, Su L, Kuhns D, Zarember KA, Peshwa MV, Malech HL (2017) CRISPR-Cas9 gene repair of hematopoietic stem cells from patients with X-linked chronic granulomatous disease. Sci Transl Med 9(372):eaah3480. https://doi.org/10.1126/scitranslmed.aah3480
Decoursey TE, Ligeti E (2005) Regulation and termination of NADPH oxidase activity. Cell Mol Life Sci 62(19–20):2173–2193. https://doi.org/10.1007/s00018-005-5177-1
Dhillon SS, Fattouh R, Elkadri A, Xu W, Murchie R, Walters T, Guo C, Mack D, Huynh HQ, Baksh S, Silverberg MS, Griffiths AM, Snapper SB, Brumell JH, Muise AM (2014) Variants in nicotinamide adenine dinucleotide phosphate oxidase complex components determine susceptibility to very early onset inflammatory bowel disease. Gastroenterology 147(3):680–689 e682. https://doi.org/10.1053/j.gastro.2014.06.005
Dinauer MC (2019) Inflammatory consequences of inherited disorders affecting neutrophil function. Blood 133(20):2130–2139. https://doi.org/10.1182/blood-2018-11-844563
Donko A, Morand S, Korzeniowska A, Boudreau HE, Zana M, Hunyady L, Geiszt M, Leto TL (2014) Hypothyroidism-associated missense mutation impairs NADPH oxidase activity and intracellular trafficking of Duox2. Free Radic Biol Med 73:190–200. https://doi.org/10.1016/j.freeradbiomed.2014.05.006
Dufort G, Larrivee-Vanier S, Eugene D, De Deken X, Seebauer B, Heinimann K, Levesque S, Gravel S, Szinnai G, Van Vliet G, Deladoey J (2019) Wide spectrum of DUOX2 deficiency: from life-threatening compressive goiter in infancy to lifelong euthyroidism. Thyroid 29(7):1018–1022. https://doi.org/10.1089/thy.2018.0461
Egea L, Hirata Y, Kagnoff MF (2010) GM-CSF: a role in immune and inflammatory reactions in the intestine. Expert Rev Gastroenterol Hepatol 4(6):723–731. https://doi.org/10.1586/egh.10.73
El-Benna J, Hurtado-Nedelec M, Marzaioli V, Marie JC, Gougerot-Pocidalo MA, Dang PM (2016) Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol Rev 273(1):180–193. https://doi.org/10.1111/imr.12447
Falcone EL, Holland SM (2019) Gastrointestinal complications in chronic granulomatous disease. Methods Mol Biol 1982:573–586. https://doi.org/10.1007/978-1-4939-9424-3_34
Fernandez-Boyanapalli R, Frasch SC, Riches DW, Vandivier RW, Henson PM, Bratton DL (2010) PPARgamma activation normalizes resolution of acute sterile inflammation in murine chronic granulomatous disease. Blood 116(22):4512–4522. https://doi.org/10.1182/blood-2010-02-272005
Fernandez-Boyanapalli RF, Falcone EL, Zerbe CS, Marciano BE, Frasch SC, Henson PM, Holland SM, Bratton DL (2015a) Impaired efferocytosis in human chronic granulomatous disease is reversed by pioglitazone treatment. J Allergy Clin Immunol 136(5):1399–1401 e1393. https://doi.org/10.1016/j.jaci.2015.07.034
Fernandez-Boyanapalli RF, Frasch SC, Thomas SM, Malcolm KC, Nicks M, Harbeck RJ, Jakubzick CV, Nemenoff R, Henson PM, Holland SM, Bratton DL (2015b) Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal capacity in chronic granulomatous disease. J Allergy Clin Immunol 135(2):517–527 e512. https://doi.org/10.1016/j.jaci.2014.10.034
Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194(1):7–15. https://doi.org/10.1083/jcb.201102095
Giannoni E, Buricchi F, Raugei G, Ramponi G, Chiarugi P (2005) Intracellular reactive oxygen species activate Src tyrosine kinase during cell adhesion and anchorage-dependent cell growth. Mol Cell Biol 25(15):6391–6403. https://doi.org/10.1128/MCB.25.15.6391-6403.2005
Gilroy S, Bialasek M, Suzuki N, Gorecka M, Devireddy AR, Karpinski S, Mittler R (2016) ROS, calcium, and electric signals: key mediators of rapid systemic signaling in plants. Plant Physiol 171(3):1606–1615. https://doi.org/10.1104/pp.16.00434
Giridharan SS, Caplan S (2014) MICAL-family proteins: complex regulators of the actin cytoskeleton. Antioxid Redox Signal 20(13):2059–2073. https://doi.org/10.1089/ars.2013.5487
Goitre L, De Luca E, Braggion S, Trapani E, Guglielmotto M, Biasi F, Forni M, Moglia A, Trabalzini L, Retta SF (2014) KRIT1 loss of function causes a ROS-dependent upregulation of c-Jun. Free Radic Biol Med 68:134–147. https://doi.org/10.1016/j.freeradbiomed.2013.11.020
Grasberger H, De Deken X, Mayo OB, Raad H, Weiss M, Liao XH, Refetoff S (2012) Mice deficient in dual oxidase maturation factors are severely hypothyroid. Mol Endocrinol 26(3):481–492. https://doi.org/10.1210/me.2011-1320
Grasberger H, Noureldin M, Kao TD, Adler J, Lee JM, Bishu S, El-Zaatari M, Kao JY, Waljee AK (2018) Increased risk for inflammatory bowel disease in congenital hypothyroidism supports the existence of a shared susceptibility factor. Sci Rep 8(1):10158. https://doi.org/10.1038/s41598-018-28586-5
Halliwell B (2006) Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol 141(2):312–322. https://doi.org/10.1104/pp.106.077073
Hayes P, Dhillon S, O’Neill K, Thoeni C, Hui KY, Elkadri A, Guo CH, Kovacic L, Aviello G, Alvarez LA, Griffiths AM, Snapper SB, Brant SR, Doroshow JH, Silverberg MS, Peter I, McGovern DP, Cho J, Brumell JH, Uhlig HH, Bourke B, Muise AA, Knaus UG (2015) Defects in NADPH oxidase genes NOX1 and DUOX2 in very early onset inflammatory bowel disease. Cell Mol Gastroenterol Hepatol 1(5):489–502. https://doi.org/10.1016/j.jcmgh.2015.06.005
Heppner DE, Dustin CM, Liao C, Hristova M, Veith C, Little AC, Ahlers BA, White SL, Deng B, Lam YW, Li J, van der Vliet A (2018) Direct cysteine sulfenylation drives activation of the Src kinase. Nat Commun 9(1):4522. https://doi.org/10.1038/s41467-018-06790-1
Hertzberger R, Arents J, Dekker HL, Pridmore RD, Gysler C, Kleerebezem M, de Mattos MJ (2014) H(2)O(2) production in species of the Lactobacillus acidophilus group: a central role for a novel NADH-dependent flavin reductase. Appl Environ Microbiol 80(7):2229–2239. https://doi.org/10.1128/AEM.04272-13
Hobbs GA, Zhou B, Cox AD, Campbell SL (2014) Rho GTPases, oxidation, and cell redox control. Small GTPases 5:e28579. https://doi.org/10.4161/sgtp.28579
Huang C, De Ravin SS, Paul AR, Heller T, Ho N, Wu Datta L, Zerbe CS, Marciano BE, Kuhns DB, Kader HA, Holland SM, Malech HL, Brant SR, Consortium NIG (2016) Genetic risk for inflammatory bowel disease is a determinant of crohn’s disease development in chronic granulomatous disease. Inflamm Bowel Dis 22(12):2794–2801. https://doi.org/10.1097/MIB.0000000000000966
Hung RJ, Pak CW, Terman JR (2011) Direct redox regulation of F-actin assembly and disassembly by Mical. Science 334(6063):1710–1713. https://doi.org/10.1126/science.1211956
Isolauri E, Kirjavainen PV, Salminen S (2002) Probiotics: a role in the treatment of intestinal infection and inflammation? Gut 50(Suppl 3):III54–III59
Jarvis RM, Hughes SM, Ledgerwood EC (2012) Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells. Free Radic Biol Med 53(7):1522–1530. https://doi.org/10.1016/j.freeradbiomed.2012.08.001
Kawahara T, Quinn MT, Lambeth JD (2007) Molecular evolution of the reactive oxygen-generating NADPH oxidase (Nox/Duox) family of enzymes. BMC Evol Biol 7:109. 1471-2148-7-109 [pii]. https://doi.org/10.1186/1471-2148-7-109
Knaus UG, Hertzberger R, Pircalabioru GG, Yousefi SP, Branco Dos Santos F (2017) Pathogen control at the intestinal mucosa – H2O2 to the rescue. Gut Microbes 8(1):67–74. https://doi.org/10.1080/19490976.2017.1279378
Kohn DB, Booth C, Kang EM, Pai SY, Shaw KL, Santilli G, Armant M, Buckland KF, Choi U, De Ravin SS, Dorsey MJ, Kuo CY, Leon-Rico D, Rivat C, Izotova N, Gilmour K, Snell K, Dip JX, Darwish J, Morris EC, Terrazas D, Wang LD, Bauser CA, Paprotka T, Kuhns DB, Gregg J, Raymond HE, Everett JK, Honnet G, Biasco L, Newburger PE, Bushman FD, Grez M, Gaspar HB, Williams DA, Malech HL, Galy A, Thrasher AJ, Net CGDc (2020) Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat Med 26(2):200–206. https://doi.org/10.1038/s41591-019-0735-5
Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, Uzel G, DeRavin SS, Priel DA, Soule BP, Zarember KA, Malech HL, Holland SM, Gallin JI (2010) Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med 363(27):2600–2610. https://doi.org/10.1056/NEJMoa1007097
Leoni G, Alam A, Neumann PA, Lambeth JD, Cheng G, McCoy J, Hilgarth RS, Kundu K, Murthy N, Kusters D, Reutelingsperger C, Perretti M, Parkos CA, Neish AS, Nusrat A (2013) Annexin A1, formyl peptide receptor, and NOX1 orchestrate epithelial repair. J Clin Invest 123(1):443–454. https://doi.org/10.1172/JCI65831
Li XJ, Goodwin CB, Nabinger SC, Richine BM, Yang Z, Hanenberg H, Ohnishi H, Matozaki T, Feng GS, Chan RJ (2015) Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst. J Biol Chem 290(7):3894–3909. https://doi.org/10.1074/jbc.M114.614057
Lievin-Le Moal V, Servin AL (2014) Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents. Clin Microbiol Rev 27(2):167–199. https://doi.org/10.1128/CMR.00080-13
Liu H, Nishitoh H, Ichijo H, Kyriakis JM (2000) Activation of apoptosis signal-regulating kinase 1 (ASK1) by tumor necrosis factor receptor-associated factor 2 requires prior dissociation of the ASK1 inhibitor thioredoxin. Mol Cell Biol 20(6):2198–2208. https://doi.org/10.1128/mcb.20.6.2198-2208.2000
Marciano BE, Zerbe CS, Falcone EL, Ding L, DeRavin SS, Daub J, Kreuzburg S, Yockey L, Hunsberger S, Foruraghi L, Barnhart LA, Matharu K, Anderson V, Darnell DN, Frein C, Fink DL, Lau KP, Long Priel DA, Gallin JI, Malech HL, Uzel G, Freeman AF, Kuhns DB, Rosenzweig SD, Holland SM (2018) X-linked carriers of chronic granulomatous disease: illness, lyonization, and stability. J Allergy Clin Immunol 141(1):365–371. https://doi.org/10.1016/j.jaci.2017.04.035
McElroy GS, Chandel NS (2017) Mitochondria control acute and chronic responses to hypoxia. Exp Cell Res 356(2):217–222. https://doi.org/10.1016/j.yexcr.2017.03.034
Merling RK, Kuhns DB, Sweeney CL, Wu X, Burkett S, Chu J, Lee J, Koontz S, Di Pasquale G, Afione SA, Chiorini JA, Kang EM, Choi U, De Ravin SS, Malech HL (2017) Gene-edited pseudogene resurrection corrects p47(phox)-deficient chronic granulomatous disease. Blood Adv 1(4):270–278. https://doi.org/10.1182/bloodadvances.2016001214
Moreno JC, Bikker H, Kempers MJ, van Trotsenburg AS, Baas F, de Vijlder JJ, Vulsma T, Ris-Stalpers C (2002) Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N Engl J Med 347(2):95–102. https://doi.org/10.1056/NEJMoa012752
Moura FA, de Andrade KQ, dos Santos JC, Araujo OR, Goulart MO (2015) Antioxidant therapy for treatment of inflammatory bowel disease: does it work? Redox Biol 6:617–639. https://doi.org/10.1016/j.redox.2015.10.006
Nadeau PJ, Charette SJ, Toledano MB, Landry J (2007) Disulfide bond-mediated multimerization of Ask1 and its reduction by thioredoxin-1 regulate H(2)O(2)-induced c-Jun NH(2)-terminal kinase activation and apoptosis. Mol Biol Cell 18(10):3903–3913. https://doi.org/10.1091/mbc.e07-05-0491
Nadella M, Bianchet MA, Gabelli SB, Barrila J, Amzel LM (2005) Structure and activity of the axon guidance protein MICAL. Proc Natl Acad Sci U S A 102(46):16830–16835. https://doi.org/10.1073/pnas.0504838102
Nauseef WM (2019) The phagocyte NOX2 NADPH oxidase in microbial killing and cell signaling. Curr Opin Immunol 60:130–140. https://doi.org/10.1016/j.coi.2019.05.006
O’Neill S, Brault J, Stasia MJ, Knaus UG (2015) Genetic disorders coupled to ROS deficiency. Redox Biol 6:135–156. https://doi.org/10.1016/j.redox.2015.07.009
Oakley FD, Abbott D, Li Q, Engelhardt JF (2009) Signaling components of redox active endosomes: the redoxosomes. Antioxid Redox Signal 11(6):1313–1333. https://doi.org/10.1089/ARS.2008.2363
Ohye H, Sugawara M (2010) Dual oxidase, hydrogen peroxide and thyroid diseases. Exp Biol Med (Maywood) 235(4):424–433. https://doi.org/10.1258/ebm.2009.009241
Park J, Lee S, Lee S, Kang SW (2014) 2-cys peroxiredoxins: emerging hubs determining redox dependency of mammalian signaling networks. Int J Cell Biol 2014:715867. https://doi.org/10.1155/2014/715867
Parkos CA (2016) Neutrophil-epithelial interactions: a double-edged sword. Am J Pathol 186(6):1404–1416. https://doi.org/10.1016/j.ajpath.2016.02.001
Parlato M, Charbit-Henrion F, Hayes P, Tiberti A, Aloi M, Cucchiara S, Begue B, Bras M, Pouliet A, Rakotobe S, Ruemmele F, Knaus UG, Cerf-Bensussan N (2017) First identification of biallelic inherited DUOX2 inactivating mutations as a cause of very early onset inflammatory bowel disease. Gastroenterology 153(2):609–611 e603. https://doi.org/10.1053/j.gastro.2016.12.053
Paulsen CE, Carroll KS (2013) Cysteine-mediated redox signaling: chemistry, biology, and tools for discovery. Chem Rev 113(7):4633–4679. https://doi.org/10.1021/cr300163e
Peters C, Nicholas AK, Schoenmakers E, Lyons G, Langham S, Serra EG, Sebire NJ, Muzza M, Fugazzola L, Schoenmakers N (2019) DUOX2/DUOXA2 mutations frequently cause congenital hypothyroidism that evades detection on newborn screening in the United Kingdom. Thyroid 29(6):790–801. https://doi.org/10.1089/thy.2018.0587
Pircalabioru G, Aviello G, Kubica M, Zhdanov A, Paclet MH, Brennan L, Hertzberger R, Papkovsky D, Bourke B, Knaus UG (2016) Defensive mutualism rescues NADPH oxidase inactivation in gut infection. Cell Host Microbe 19(5):651–663. https://doi.org/10.1016/j.chom.2016.04.007
Poole LB, Nelson KJ (2016) Distribution and features of the six classes of peroxiredoxins. Mol Cells 39(1):53–59. https://doi.org/10.14348/molcells.2016.2330
Pryor WA (1986) Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol 48:657–667. https://doi.org/10.1146/annurev.ph.48.030186.003301
Radi R (2018) Oxygen radicals, nitric oxide, and peroxynitrite: redox pathways in molecular medicine. Proc Natl Acad Sci U S A 115(23):5839–5848. https://doi.org/10.1073/pnas.1804932115
Randall LM, Manta B, Hugo M, Gil M, Batthyany C, Trujillo M, Poole LB, Denicola A (2014) Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase. J Biol Chem 289(22):15536–15543. https://doi.org/10.1074/jbc.M113.539213
Reid G (2008) Probiotic lactobacilli for urogenital health in women. J Clin Gastroenterol 42(Suppl 3 Pt 2):S234–S236. https://doi.org/10.1097/MCG.0b013e31817f1298
Rhee SG, Kil IS (2016) Mitochondrial H2O2 signaling is controlled by the concerted action of peroxiredoxin III and sulfiredoxin: linking mitochondrial function to circadian rhythm. Free Radic Biol Med 99:120–127. https://doi.org/10.1016/j.freeradbiomed.2016.07.029
Roos D (2016) Chronic granulomatous disease. Br Med Bull 118(1):50–63. https://doi.org/10.1093/bmb/ldw009
Rousset B, Dupuy C, Miot F, Dumont J (2000) Chapter 2 thyroid hormone synthesis and secretion. In: Feingold KR, Anawalt B, Boyce A et al (eds) Endotext. MDtext, South Dartmouth
Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24(10):R453–R462. https://doi.org/10.1016/j.cub.2014.03.034
Schwerd T, Bryant RV, Pandey S, Capitani M, Meran L, Cazier JB, Jung J, Mondal K, Parkes M, Mathew CG, Fiedler K, McCarthy DJ, Consortium WGS, Sullivan PB, Rodrigues A, Travis SPL, Moore C, Sambrook J, Ouwehand WH, Roberts DJ, Danesh J, Study I, Russell RK, Wilson DC, Kelsen JR, Cornall R, Denson LA, Kugathasan S, Knaus UG, Serra EG, Anderson CA, Duerr RH, McGovern DP, Cho J, Powrie F, Li VS, Muise AM, Uhlig HH, Oxford IBDcsi, investigators CiIg, Consortium UIG (2018) NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease. Mucosal Immunol 11(2):562–574. https://doi.org/10.1038/mi.2017.74
Sherid M, Samo S, Sulaiman S, Husein H, Sifuentes H, Sridhar S (2016) Liver abscess and bacteremia caused by lactobacillus: role of probiotics? Case report and review of the literature. BMC Gastroenterol 16(1):138. https://doi.org/10.1186/s12876-016-0552-y
Sies H (1993) Strategies of antioxidant defense. Eur J Biochem 215(2):213–219
Singh AK, Hertzberger RY, Knaus UG (2018) Hydrogen peroxide production by lactobacilli promotes epithelial restitution during colitis. Redox Biol 16:11–20. https://doi.org/10.1016/j.redox.2018.02.003
Sobotta MC, Liou W, Stocker S, Talwar D, Oehler M, Ruppert T, Scharf AN, Dick TP (2015) Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat Chem Biol 11(1):64–70. https://doi.org/10.1038/nchembio.1695
Stenke E, Bourke B, Knaus UG (2019) NAPDH oxidases in inflammatory bowel disease. Methods Mol Biol 1982:695–713. https://doi.org/10.1007/978-1-4939-9424-3_38
Stocker S, Maurer M, Ruppert T, Dick TP (2018a) A role for 2-Cys peroxiredoxins in facilitating cytosolic protein thiol oxidation. Nat Chem Biol 14(2):148–155. https://doi.org/10.1038/nchembio.2536
Stocker S, Van Laer K, Mijuskovic A, Dick TP (2018b) The conundrum of hydrogen peroxide signaling and the emerging role of peroxiredoxins as redox relay hubs. Antioxid Redox Signal 28(7):558–573. https://doi.org/10.1089/ars.2017.7162
Sumimoto H (2008) Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J 275(13):3249–3277. https://doi.org/10.1111/j.1742-4658.2008.06488.x
Sweeney CL, Merling RK, De Ravin SS, Choi U, Malech HL (2019) Gene editing in chronic granulomatous disease. Methods Mol Biol 1982:623–665. https://doi.org/10.1007/978-1-4939-9424-3_36
Tonks NK (2013) Protein tyrosine phosphatases--from housekeeping enzymes to master regulators of signal transduction. FEBS J 280(2):346–378. https://doi.org/10.1111/febs.12077
Travasso RDM, Sampaio Dos Aidos F, Bayani A, Abranches P, Salvador A (2017) Localized redox relays as a privileged mode of cytoplasmic hydrogen peroxide signaling. Redox Biol 12:233–245. https://doi.org/10.1016/j.redox.2017.01.003
Truong TH, Carroll KS (2013) Redox regulation of protein kinases. Crit Rev Biochem Mol Biol 48(4):332–356. https://doi.org/10.3109/10409238.2013.790873
Vahabnezhad E, Mochon AB, Wozniak LJ, Ziring DA (2013) Lactobacillus bacteremia associated with probiotic use in a pediatric patient with ulcerative colitis. J Clin Gastroenterol 47(5):437–439. https://doi.org/10.1097/MCG.0b013e318279abf0
Vestergaard CL, Flyvbjerg H, Moller IM (2012) Intracellular signaling by diffusion: can waves of hydrogen peroxide transmit intracellular information in plant cells? Front Plant Sci 3:295. https://doi.org/10.3389/fpls.2012.00295
von Lohneysen K, Noack D, Wood MR, Friedman JS, Knaus UG (2010) Structural insights into Nox4 and Nox2: motifs involved in function and cellular localization. Mol Cell Biol 30(4):961–975. https://doi.org/10.1128/MCB.01393-09
Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4(5):278–286. https://doi.org/10.1038/nchembio.85
Winterbourn CC (2013) The biological chemistry of hydrogen peroxide. Methods Enzymol 528:3–25. https://doi.org/10.1016/B978-0-12-405881-1.00001-X
Winterbourn CC, Peskin AV (2016) Kinetic approaches to measuring peroxiredoxin reactivity. Mol Cells 39(1):26. https://doi.org/10.14348/molcells.2016.2325
Woo HA, Yim SH, Shin DH, Kang D, Yu DY, Rhee SG (2010) Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. Cell 140(4):517–528. https://doi.org/10.1016/j.cell.2010.01.009
Xu D, Zheng H, Yu WM, Qu CK (2013) Activating mutations in protein tyrosine phosphatase Ptpn11 (Shp2) enhance reactive oxygen species production that contributes to myeloproliferative disorder. PLoS One 8(5):e63152. https://doi.org/10.1371/journal.pone.0063152
Zana M, Peterfi Z, Kovacs HA, Toth ZE, Enyedi B, Morel F, Paclet MH, Donko A, Morand S, Leto TL, Geiszt M (2018) Interaction between p22(phox) and Nox4 in the endoplasmic reticulum suggests a unique mechanism of NADPH oxidase complex formation. Free Radic Biol Med 116:41–49. https://doi.org/10.1016/j.freeradbiomed.2017.12.031
Zhang H, Forman HJ (2014) TGFbeta1 rapidly activates Src through a non-canonical redox mechanism. Free Radic Biol Med 75(Suppl 1):S4. https://doi.org/10.1016/j.freeradbiomed.2014.10.831
Zhou Y, An LL, Chaerkady R, Mittereder N, Clarke L, Cohen TS, Chen B, Hess S, Sims GP, Mustelin T (2018) Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils. Sci Rep 8(1):15228. https://doi.org/10.1038/s41598-018-33385-z
Acknowledgments
Our work has been primarily supported by the National Institutes of Health (USA), Science Foundation Ireland, and the National Children’s Research Center (both Ireland). I would like to thank William M. Nauseef, University of Iowa, for critical review, and colleagues in the NOX field and in EU-ROS, a European Network for Redox Biology Research, for stimulating discussions over the years.
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Knaus, U.G. (2020). Oxidants in Physiological Processes. In: Schmidt, H.H.H.W., Ghezzi, P., Cuadrado, A. (eds) Reactive Oxygen Species . Handbook of Experimental Pharmacology, vol 264. Springer, Cham. https://doi.org/10.1007/164_2020_380
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