title: Disruption of ion-trafficking system in the cochlear spiral ligament prior to permanent hearing loss induced by exposure to intense noise: possible involvement of 4-hydroxy-2-nonenal as a mediator of oxidative stress.
abstract: Noise-induced hearing loss is at least in part due to disruption of endocochlear potential, which is maintained by various K(+) transport apparatuses including Na(+), K(+)-ATPase and gap junction-mediated intercellular communication in the lateral wall structures. In this study, we examined the changes in the ion-trafficking-related proteins in the spiral ligament fibrocytes (SLFs) following in vivo acoustic overstimulation or in vitro exposure of cultured SLFs to 4-hydroxy-2-nonenal, which is a mediator of oxidative stress. Connexin (Cx)26 and Cx30 were ubiquitously expressed throughout the spiral ligament, whereas Na(+), K(+)-ATPase α1 was predominantly detected in the stria vascularis and spiral prominence (type 2 SLFs). One-hour exposure of mice to 8 kHz octave band noise at a 110 dB sound pressure level produced an immediate and prolonged decrease in the Cx26 expression level and in Na+, K(+)-ATPase activity, as well as a delayed decrease in Cx30 expression in the SLFs. The noise-induced hearing loss and decrease in the Cx26 protein level and Na(+), K(+)-ATPase activity were abolished by a systemic treatment with a free radical-scavenging agent, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, or with a nitric oxide synthase inhibitor, N(ω)-nitro-L-arginine methyl ester hydrochloride. In vitro exposure of SLFs in primary culture to 4-hydroxy-2-nonenal produced a decrease in the protein levels of Cx26 and Na(+), K(+)-ATPase α1, as well as Na(+), K(+)-ATPase activity, and also resulted in dysfunction of the intercellular communication between the SLFs. Taken together, our data suggest that disruption of the ion-trafficking system in the cochlear SLFs is caused by the decrease in Cxs level and Na(+), K(+)-ATPase activity, and at least in part involved in permanent hearing loss induced by intense noise. Oxidative stress-mediated products might contribute to the decrease in Cxs content and Na(+), K(+)-ATPase activity in the cochlear lateral wall structures.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagashima
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoneyama
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Shiba
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Ogita
mesh_terms: D000447:Aldehydes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D061251:Primary Cell Culture; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D055493:Spiral Ligament of Cochlea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013316:Stria Vascularis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C110289:4-hydroxy-2,2,6,6--tetramethylpiperidine-1-N-hydroxyl; D000447:Aldehydes; D000075302:Connexin 30; D017630:Connexins; D016166:Free Radical Scavengers; D005609:Free Radicals; C100629:Gjb6 protein, mouse; D010880:Piperidines; D000072259:Connexin 26; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase; C027576:4-hydroxy-2-nonenal; D019331:NG-Nitroarginine Methyl Ester