Age-related changes in the ratio of Mcl-1/Bax expression in the rat cochlea

Abstract

Conclusion: Down-regulation of the ratio of Mcl-1/Bax expression may contribute to age-related sensory cell degeneration in the cochlea. Objective: To better understand the involvement of Bcl-2 family members in the regulation of age-related sensory cell death, we examined the expression patterns of Bcl-2-associated protein X (Bax) and its suppressor, myeloid cell leukemia 1 (Mcl-1) in young and aging rat cochleae. Methods: Young (2–3 months) and aging (27–28 months) Fischer rats were used. The auditory brainstem response (ABR) thresholds elicited by tone bursts at 4, 8, 16, 32, and 40 kHz were measured. The expression patterns of Mcl-1 and Bax genes at both the mRNA and protein levels were examined using a real-time RT-PCR assay and Western blot. Distribution of Mcl-1 and Bax expression in the cochlear sensory epithelia was evaluated using immunohistology and nuclear staining. Results: Aging cochleae exhibited a significant elevation of ABR thresholds. This change was accompanied by significant reduction in Mcl-1 expression at both the mRNA and the protein levels and in the ratio of expression levels of Mcl-1/Bax genes in the aging subjects. Importantly, the changes in Mcl-1 and Bax expression are spatially related to the sensory cells showing the sign of degeneration.

Keywords::

• Aging
• hair cell
• apoptosis
• degeneration

Acknowledgment

This study was supported by grants from the National Natural Science Foundation of China (no. 30973304).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.