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

Autor:	Kaoru Goto, Yasukazu Hozumi, Seiji Kakehata, Makoto Chiba, Hirooki Matsui, Tsukasa Ito, Chikako Shinkawa
Rok vydání:	2019
Předmět:	0301 basic medicine Diacylglycerol Kinase Histology Guinea Pigs 03 medical and health sciences Stress Physiological otorhinolaryngologic diseases medicine Animals Mechanotransduction Molecular Biology Spiral ganglion Cochlea Diacylglycerol kinase 030102 biochemistry & molecular biology Chemistry Cell Biology Cell biology Intracellular signal transduction Medical Laboratory Technology 030104 developmental biology medicine.anatomical_structure Second messenger system sense organs Hair cell Signal transduction Noise
Zdroj:	Histochemistry and Cell Biology. 151:461-474
ISSN:	1432-119X 0948-6143
DOI:	10.1007/s00418-019-01781-9
Popis:	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.
Databáze:	OpenAIRE
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