NOX3, a Superoxide-generating NADPH Oxidase of the Inner Ear
| Autor: | Botond Banfi, Brigitte Malgrange, Klaus Steger, Judit Knisz, Karl-Heinz Krause, Michel Dubois-Dauphin |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
ddc:616.07
Membrane Glycoproteins/physiology Biochemistry Rats Sprague-Dawley Mice chemistry.chemical_compound Superoxides Ear Inner/ enzymology Cells Cultured In Situ Hybridization chemistry.chemical_classification Oxidase test Membrane Glycoproteins NADPH oxidase Superoxide RNA Messenger/analysis Cell biology medicine.anatomical_structure NADPH Oxidase 2 Proteins/physiology DNA Complementary Protein subunit Molecular Sequence Data In situ hybridization Biology DNA Complementary/analysis Superoxides/ metabolism otorhinolaryngologic diseases medicine Animals Humans Inner ear RNA Messenger Molecular Biology Adaptor Proteins Signal Transducing Reactive oxygen species Base Sequence HEK 293 cells NADPH Oxidases Proteins Cell Biology Rats Mice Inbred C57BL Protein Subunits chemistry Ear Inner biology.protein sense organs NADPH Oxidase/ genetics/physiology |
| Zdroj: | Journal of Biological Chemistry, Vol. 279, No 44 (2004) pp. 46065-46072 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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