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Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions

  • Chikako Shinkawa
  • Tsukasa ItoEmail author
  • Yasukazu Hozumi
  • Makoto Chiba
  • Hirooki Matsui
  • Kaoru Goto
  • Seiji Kakehata
Original Paper
  • 35 Downloads

Abstract

Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.

Keywords

Diacylglycerol kinase Noise exposure Sensorineural hearing loss Outer hair cell Cytoplasmic translocation 

Abbreviation

DGK

Diacylglycerol kinase

IHC

Inner hair call

OHC

Outer hair cell

SC

Supporting cell

SGN

Spiral ganglion neuron

Notes

Acknowledgements

This work was supported by JSPS KAKENHI Grant Numbers JP15K20178 to HM, JP15K20179 to CS and JP17K11313 to TI.

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Copyright information

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

Authors and Affiliations

  1. 1.Department of Otolaryngology, Head and Neck SurgeryYamagata University Faculty of MedicineYamagata-shiJapan
  2. 2.Department of Cell Biology and MorphologyAkita University Graduate School of MedicineAkitaJapan
  3. 3.Department of Anatomy and Cell BiologyYamagata University Faculty of MedicineYamagataJapan

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