title: Roles of DUOX-mediated hydrogen peroxide in metabolism, host defense, and signaling.
abstract: CONCLUSIONS
  Among the NADPH oxidases, the dual oxidases, DUOX1 and DUOX2, constitute a distinct subfamily initially called thyroid oxidases, based on their high level of expression in thyroid tissue. Genetic alterations causing inherited hypothyroidism clearly demonstrate their physiological implication in thyroid hormonogenesis. However, a growing list of biological functions triggered by DUOX-dependent reactive oxygen species (ROS) in highly differentiated mucosae have recently emerged.
  
  
  BACKGROUND
  A role of DUOX enzymes as ROS providers for lactoperoxidase-mediated killing of invading pathogens has been well established and a role in bacteria chemorepulsion has been proposed. Control of DUOX expression and activity by inflammatory molecules and immune receptor activation consolidates their contributions to innate immune defense of mucosal surfaces. Recent studies conducted in ancestral organisms have identified effectors of DUOX redox signaling involved in wound healing including epithelium regeneration and leukocyte recruitment. Moreover, local generation of hydrogen peroxide (H2O2) by DUOX has also been suggested to constitute a positive feedback loop to promote receptor signaling activation.
  
  
  RESULTS
  A correct balance between H2O2 generation and detoxification mechanisms must be properly maintained to avoid oxidative damages. Overexpression of DUOX genes has been associated with an increasing number of chronic inflammatory diseases. Furthermore, H2O2-mediated DNA damage supports a mutagenic function promoting tumor development.
  
  
  CONCLUSIONS
  Despite the high sequence similarity shared between DUOX1 and DUOX2, the two isoforms present distinct regulations, tissue expression and catalytic functions. The phenotypic characterization of novel DUOX/DUOXA invalidated animal models will be very useful for defining their medical importance in pathological conditions.
authors.affiliation: Faculté de Médecine, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM), Université Libre de Bruxelles (ULB) , Brussels, Belgium .
authors.forename: Xavier
authors.initials: X
authors.lastname: De Deken
authors.forename: Bernard
authors.initials: B
authors.lastname: Corvilain
authors.forename: Jacques Emile
authors.initials: JE
authors.lastname: Dumont
authors.forename: Françoise
authors.initials: F
authors.lastname: Miot
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D000074623:Dual Oxidases; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D023421:Models, Animal; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; C431515:DUOX2 protein, human