NOX3, a superoxide-generating NADPH oxidase of the inner ear

Botond Bánfi; Brigitte Malgrange; Judit Knisz; Klaus Steger; Michel Dubois-Dauphin; Karl-Heinz Krause

doi:10.1074/jbc.M403046200

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NOX3, a superoxide-generating NADPH oxidase of the inner ear

Journal article

Open access

Peer reviewed

NOX3, a superoxide-generating NADPH oxidase of the inner ear

Botond Bánfi, Brigitte Malgrange, Judit Knisz, Klaus Steger, Michel Dubois-Dauphin and Karl-Heinz Krause

The Journal of biological chemistry, Vol.279(44), pp.46065-46072

10/29/2004

DOI: 10.1074/jbc.M403046200

PMID: 15326186

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Abstract

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.

Adaptor Proteins, Signal Transducing

Animals

Base Sequence

Cells, Cultured

DNA, Complementary - analysis

Ear, Inner - enzymology

Humans

In Situ Hybridization

Membrane Glycoproteins - physiology

Mice

Mice, Inbred C57BL

Molecular Sequence Data

NADPH Oxidase 2

NADPH Oxidases - genetics

NADPH Oxidases - physiology

Protein Subunits

Proteins - physiology

Rats

Rats, Sprague-Dawley

RNA, Messenger - analysis

Superoxides - metabolism

Details

Title: Subtitle: NOX3, a superoxide-generating NADPH oxidase of the inner ear
Creators: Botond Bánfi - University of Iowa
Brigitte Malgrange - University of Liège
Judit Knisz - Department of Anatomy and Cell Biology and
Klaus Steger - Institute of Veterinary Anatomy, 35392 Giessen, Germany, and
Michel Dubois-Dauphin - University of Geneva
Karl-Heinz Krause - University of Geneva
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(44), pp.46065-46072
DOI: 10.1074/jbc.M403046200
PMID: 15326186
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: R01 AI020866 / NIAID NIH HHS AG19519-01 / NIA NIH HHS R01 AG019519 / NIA NIH HHS AI20866-18 / NIAID NIH HHS
Language: English
Date published: 10/29/2004
Academic Unit: Anatomy and Cell Biology; Otolaryngology; Internal Medicine
Record Identifier: 9984284359302771

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