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

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.