Archives of Toxicology

, Volume 93, Issue 11, pp 3219–3228 | Cite as

Heat shock protein 70 is a key molecule to rescue imbalance caused by low-frequency noise

  • Reina Negishi-Oshino
  • Nobutaka Ohgami
  • Tingchao He
  • Xiang Li
  • Masashi Kato
  • Masayoshi Kobayashi
  • Yishuo Gu
  • Kanako Komuro
  • Charalampos E. Angelidis
  • Masashi KatoEmail author
Molecular Toxicology


A previous study showed that people living in urban areas are generally exposed to low-frequency noise (LFN) with frequencies below 100 Hz and sound levels of 60–110 dB in daily and occupational environments. Exposure to LFN has been shown to affect balance in humans and mice. However, there is no information about prevention of LFN-mediated imbalance because of a lack of information about the target region based on health risk assessment of LFN exposure. Here, we show that acute exposure to LFN at 100 Hz, 95 dB, but not at 85 dB or 90 dB, for only 1 h caused imbalance in mice. The exposed mice also had decreased cervical vestibular-evoked myogenic potential (cVEMP) with impaired activity of vestibular hair cells. Since imbalance in the exposed mice was irreversible, morphological damage in the vestibules of the exposed mice was further examined. The exposed mice had breakage of the otoconial membrane in the vestibule. LFN-mediated imbalance and breakage of the otoconial membrane in mice were rescued by overexpression of a stress-reactive molecular chaperone, heat shock protein 70 (Hsp70), which has been shown to be induced by exposure of mice to 12 h per day of LFN at 95 dB for 5 days. Taken together, the results of this study demonstrate that acute exposure to LFN at 100 Hz, 95 dB for only 1 h caused irreversible imbalance in mice with structural damage of the otoconial membrane as the target region for LFN-mediated imbalance, which can be rescued by Hsp70.


HSP70 Low-frequency noise Otoconial membrane cVEMP Balance 



This study was supported in part by Grants-in-Aid for Scientific Research on Innovative Areas (16H01639 and 18H04975), Scientific Research (A) (15H01743, 15H02588, and 19H01147), (B) (17KT0033) and (C) (25460178, 16K08343, and 17K09156) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Mirai-Program Small Start Type from the Japan Science and Technology Agency (JST), DAIKO FOUNDATION, Kobayashi International Scholarship Foundation and AEON Environmental Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare to have no actual or potential conflicts of interest.

Supplementary material

204_2019_2587_MOESM1_ESM.pdf (5.6 mb)
Supplementary material 1 (PDF 5729 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Reina Negishi-Oshino
    • 1
  • Nobutaka Ohgami
    • 1
  • Tingchao He
    • 1
  • Xiang Li
    • 1
  • Masashi Kato
    • 2
  • Masayoshi Kobayashi
    • 3
  • Yishuo Gu
    • 1
  • Kanako Komuro
    • 1
  • Charalampos E. Angelidis
    • 4
  • Masashi Kato
    • 1
    Email author
  1. 1.Department of Occupational and Environmental HealthNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Electrical and Mechanical EngineeringNagoya Institute of TechnologyNagoyaJapan
  3. 3.EPMA LaboratoryNiigata University Center for Instrumental AnalysisNiigataJapan
  4. 4.General Biology, Medical SchoolUniversity of IoanninaIoanninaGreece

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