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Age-related changes in the ratio of Mcl-1/Bax expression in the rat cochlea
Wei Ping Yang1, Wei Wei Guo, Hui Zhan Liu
1Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, PR China. yangwp2002@yahoo.com
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.
