Degradation and modification of cochlear gap junction proteins in the early development of age-related hearing loss

Autor: Kazusaku Kamiya, Keiko Danzaki, Katsuhisa Ikeda, Shori Tajima
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Experimental and Molecular Medicine, Vol 52, Iss 1, Pp 166-175 (2020)
Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
Popis: 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.
Hearing loss: Disruption at the junction A decrease in the levels of connexin proteins at the junctions connecting cells in the inner-ear precedes age-related hearing loss (ARHL) in mice. Loss of hearing in the elderly is a growing problem in ageing populations. Although mutations in genes encoding connexins have been associated with hereditary hearing loss, their role in ARHL is poorly understood. Kazusaku Kamiya and colleagues at Juntendo University, Tokyo, found that the levels of connexin 26 and connexin 30 were significantly reduced in the cochlea in the inner ear of 32-week old mice compared to 4-week old mice. Connexin 26 also became less soluble with age. The authors suggest that these changes could lead to the degeneration and loss of function of hair cells in the cochlea, and that targeting connexin 26 could lead to new therapies for ARHL.
Databáze: OpenAIRE
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