Age-related changes in the ratio of Mcl-1/Bax expression in the rat cochlea.
CONCLUSIONS
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.
Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, PR China. yangwp2002@yahoo.com
Wei Ping
WP
Yang
Wei Wei
WW
Guo
Hui Zhan
HZ
Liu
Yang
Y
Xu
Lei
L
Chen
Bo Hua
BH
Hu
D000375:Aging / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D003051:Cochlea / Q000378:metabolism*; D015536:Down-Regulation; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D015870:Gene Expression; D006198:Hair Cells, Auditory / Q000378:metabolism / Q000473:pathology; D034381:Hearing Loss / Q000503:physiopathology; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
C494828:Bax protein, rat; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein