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: Taro Yamaguchi, Reiko Nagashima, Masanori Yoneyama, Tatsuo Shiba, Kiyokazu Ogita
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e102133 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25013956 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-hydroxy-2,2,6,6--tetramethylpiperidine-1-N-hydroxyl
• Aldehydes
• Connexin 30
• Connexins
• Free Radical Scavengers
• Free Radicals
• Gjb6 protein, mouse
• Piperidines
• Connexin 26
• Nitric Oxide Synthase Type I
• Nos1 protein, mouse
• Atp1a1 protein, mouse
• Sodium-Potassium-Exchanging ATPase
• 4-hydroxy-2-nonenal
• NG-Nitroarginine Methyl Ester

Topics

• Aldehydes (antagonists & inhibitors, pharmacology)
• Animals
• Cell Communication (drug effects)
• Connexin 26
• Connexin 30
• Connexins (antagonists & inhibitors, genetics, metabolism)
• Free Radical Scavengers (pharmacology)
• Free Radicals (antagonists & inhibitors, metabolism)
• Gene Expression Regulation
• Hearing Loss, Noise-Induced (etiology, genetics, metabolism, prevention & control)
• Ion Transport (drug effects)
• Male
• Mice
• Mice, Transgenic
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase Type I (antagonists & inhibitors, genetics, metabolism)
• Noise (adverse effects)
• Oxidative Stress (drug effects)
• Piperidines (pharmacology)
• Primary Cell Culture
• Signal Transduction
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, genetics, metabolism)
• Spiral Ligament of Cochlea (drug effects, metabolism, pathology)
• Stria Vascularis (drug effects, metabolism, pathology)