Reference : NOX3, a superoxide-generating NADPH oxidase of the inner ear
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/4843
NOX3, a superoxide-generating NADPH oxidase of the inner ear
English
Banfi, Botond [University of Iowa > Department of Anatomy and Cell Biology and Inflammation Program and Dept. of Internal Medicine]
Malgrange, Brigitte mailto [Université de Liège - ULiège > > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. >]
Knisz, Judit [University of Iowa > Department of Anatomy and Cell Biology and Inflammation Program and Dept. of Internal Medicine]
Steger, Klaus [Institute of Veterinary Anatomy (Giessen)]
Dubois-Dauphin, Michel [Geneva University Hospitals > Department of Geriatrics > Biology of Ageing Laboratory]
Krause, Karl-Heinz [Geneva University Hospitals > Department of Geriatrics > Biology of Ageing Laboratory]
29-Oct-2004
Journal of Biological Chemistry
Amer Soc Biochemistry Molecular Biology Inc
279
44
46065-46072
Yes (verified by ORBi)
International
0021-9258
Bethesda
[en] inner ear ; nox3 ; cisplatin
[en] Reactive oxygen species (ROS) play a major role in drug-, noise-, and age-dependent hearing loss, but the source of ROS in the inner ear remains largely unknown. Herein, we demonstrate that NADPH oxidase (NOX) 3, a member of the NOX/dual domain oxidase family of NADPH oxidases, is highly expressed in specific portions of the inner ear. As assessed by real-time PCR, NOX3 mRNA expression in the inner ear is at least 50-fold higher than in any other tissues where its expression has been observed ( e. g. fetal kidney, brain, skull). Microdissection and in situ hybridization studies demonstrated that NOX3 is localized to the vestibular and cochlear sensory epithelia and to the spiral ganglions. Transfection of human embryonic kidney 293 cells with NOX3 revealed that it generates low levels of ROS on its own but produces high levels of ROS upon co-expression with cytoplasmic NOX subunits. NOX3-dependent superoxide production required a stimulus in the absence of subunits and upon co-expression with phagocyte NADPH oxidase subunits p47(phox) and p67(phox), but it was stimulus-independent upon co-expression with colon NADPH oxidase subunits NOX organizer 1 and NOX activator 1. Pre-incubation of NOX3-transfected human embryonic kidney 293 cells with the ototoxic drug cisplatin markedly enhanced superoxide production, in both the presence and the absence of subunits. Our data suggest that NOX3 is a relevant source of ROS generation in the cochlear and vestibular systems and that NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
Researchers ; Professionals
http://hdl.handle.net/2268/4843
10.1074/jbc.M403046200

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