title: Noise-induced changes in expression levels of NADPH oxidases in the cochlea.
abstract: NADPH oxidases are enzymes that transport electrons across the plasma membrane and generate superoxide radical from molecular oxygen. The current study investigated the expression and distribution of NOX/DUOX members of the NADPH oxidase family (NOX1-5 and DUOX1-2) in the rat cochlea and their regulation in response to noise. Wistar rats (8-10 weeks) were exposed for 24 h to band noise (8-12 kHz) at moderate (100 dB) or traumatic (110 dB) sound pressure levels (SPL). Animals exposed to ambient noise (45-55 dB SPL) served as controls. Immunohistochemistry demonstrated predominant expression of all NOX/DUOX isoforms in the sensory and supporting cells of the organ of Corti, with very limited immunoexpression in the lateral wall tissues and spiral ganglion neurons. Noise exposure induced up-regulation of NOX1 and DUOX2 in the cochlea, whereas NOX3 was down-regulated. A significant reduction in the intensity of NOX3 immunolabeling was observed in the inner sulcus region of the cochlea after exposure to noise. Post-exposure inhibition of NADPH oxidases by Diphenyleneiodonium (DPI), a broadly selective NADPH oxidase inhibitor, mitigated noise-induced hearing loss.
  
  
  CONCLUSIONS
  Noise-induced up-regulation of NOX1 and DUOX2 could be linked to cochlear injury. In contrast, down-regulation of NOX3 may represent an endogenous protective mechanism to reduce oxidative stress in the noise-exposed cochlea. Inhibition of NADPH oxidases is potentially a novel pathway for therapeutic management of noise-induced hearing loss.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. Electronic address: s.vlajkovic@auckland.ac.nz.
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Vlajkovic
authors.forename: Shelly Ching-Yu
authors.initials: SC
authors.lastname: Lin
authors.forename: Ann Chi Yan
authors.initials: AC
authors.lastname: Wong
authors.forename: Brad
authors.initials: B
authors.lastname: Wackrow
authors.forename: Peter R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000201:enzymology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016057:Evoked Potentials, Auditory, Brain Stem; D015870:Gene Expression; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009622:Noise / Q000009:adverse effects*; D009861:Onium Compounds / Q000494:pharmacology; D009925:Organ of Corti / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009861:Onium Compounds; D012333:RNA, Messenger; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; C534192:Nox3 protein, rat
keywords: ABR; BSA; DPI; DUOX; Diphenyleneiodonium; EDTA; NADPH; NDS; NIHL; PBS; PFA; RNS; ROI; ROS; RWM; auditory brainstem response; bovine serum albumin; dual domain oxidase; ethylendiamintetraacetate; nicotinamide adenine dinucleotide phosphate; noise-induced hearing loss; normal donkey serum; paraformaldehyde; phosphate buffer saline; reactive nitrogen species; reactive oxygen species; region of interest; round window membrane