Degradation and modification of cochlear gap junction proteins in the early development of age-related hearing loss
Open Access
- 27 January 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Experimental & Molecular Medicine
- Vol. 52 (1), 166-175
- https://doi.org/10.1038/s12276-020-0377-1
Abstract
Age-related hearing loss (ARHL) is the progressive, bilateral loss of high-frequency hearing in elderly people. Mutations in GJB2, encoding the cochlear gap junction protein connexin26 (Cx26), are the most frequent cause of hereditary deafness; however, a common molecular pathology between ARHL and GJB2-related hearing loss has not been reported. Here, we investigated the quantitative change in expression and molecular pathology of Cx26 in ARHL. We used C57BL/6J mice as a model of ARHL. Hearing levels that were evaluated by auditory brainstem response thresholds increased gradually between 4 and 32 weeks of age and increased sharply at 36 weeks. Gap junctions in the cochleae of 4-week-old mice had linear plaques along cell–cell junction sites. In contrast, the cochleae from 32-week-old mice had significantly shorter gap junctions. Severe hair cell loss was not observed during this period. Based on western blotting, Cx26 and connexin30 (Cx30) levels were significantly decreased at 32 weeks compared with 4 weeks. Moreover, Cx26 was more significantly enriched in the hydrophilic fraction at 4 weeks but was more significantly enriched in the hydrophobic fraction at 32 weeks, indicating an age-related conversion of this biochemical property. Thus, the hydrophobic conversion of Cx26 and disruption of gap junction proteins and plaques may be involved in the pathogenesis of ARHL and may occur before severe hair cell degeneration.Keywords
Funding Information
- MEXT | Japan Society for the Promotion of Science (18H02953, 17H04348)
- Japan Agency for Medical Research and Development (19ek0109401h0002, 15ek0109125h0001, 19ae0101050h0002)
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