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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehydes / antagonists & inhibitors
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Aldehydes / pharmacology*
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Animals
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Cell Communication / drug effects
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Connexin 26
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Connexin 30
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Connexins / antagonists & inhibitors
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Connexins / genetics
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Connexins / metabolism
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Free Radical Scavengers / pharmacology*
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Free Radicals / antagonists & inhibitors
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Free Radicals / metabolism
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Gene Expression Regulation
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Hearing Loss, Noise-Induced / etiology
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Hearing Loss, Noise-Induced / genetics
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Hearing Loss, Noise-Induced / metabolism
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Hearing Loss, Noise-Induced / prevention & control*
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Ion Transport / drug effects
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Male
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Mice
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Mice, Transgenic
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NG-Nitroarginine Methyl Ester / pharmacology*
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Nitric Oxide Synthase Type I / antagonists & inhibitors
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Nitric Oxide Synthase Type I / genetics
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Nitric Oxide Synthase Type I / metabolism
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Noise / adverse effects
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Oxidative Stress / drug effects
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Piperidines / pharmacology*
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Primary Cell Culture
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Signal Transduction
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Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
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Sodium-Potassium-Exchanging ATPase / genetics
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Sodium-Potassium-Exchanging ATPase / metabolism
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Spiral Ligament of Cochlea / drug effects
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Spiral Ligament of Cochlea / metabolism*
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Spiral Ligament of Cochlea / pathology
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Stria Vascularis / drug effects
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Stria Vascularis / metabolism
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Stria Vascularis / pathology
Substances
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4-hydroxy-2,2,6,6--tetramethylpiperidine-1-N-hydroxyl
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Aldehydes
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Connexin 30
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Connexins
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Free Radical Scavengers
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Free Radicals
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Gjb6 protein, mouse
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Piperidines
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Connexin 26
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Nitric Oxide Synthase Type I
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Nos1 protein, mouse
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Atp1a1 protein, mouse
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Sodium-Potassium-Exchanging ATPase
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4-hydroxy-2-nonenal
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NG-Nitroarginine Methyl Ester
Grants and funding
This work was supported in part by grants-in-aid for scientific research to K.O.(project# 4042) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. Additional funding was received from Setsunan University for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.