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

Age-related changes in the ratio of Mcl-1/Bax expression in the rat cochlea.
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大鼠耳蜗中 Mcl-1/Bax 表达比值的年龄相关变化

DOI:
10.3109/00016489.2011.631191
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发表时间:
2012-02
影响因子:
1.4
通讯作者:
Hu BH
Hu BH
中科院分区:
医学4区
文献类型:
--
作者:
Yang WP;Guo WW;Liu HZ;Xu Y;Chen L;Hu BH

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Mcl - 1/Bax表达比例的下调可能导致耳蜗中与年龄相关的感觉细胞退化。 为了更好地理解Bcl - 2家族成员在调控与年龄相关的感觉细胞死亡中的作用,我们检测了年轻和老年大鼠耳蜗中Bcl - 2相关蛋白X(Bax)及其抑制因子髓样细胞白血病1(Mcl - 1)的表达模式。 使用了年轻(2 - 3个月)和老年(27 - 28个月)的费希尔大鼠。测量了由4、8、16、32和40 kHz的短纯音诱发的听性脑干反应(ABR)阈值。使用实时逆转录聚合酶链反应(RT - PCR)分析和蛋白质印迹法检测了Mcl - 1和Bax基因在信使核糖核酸(mRNA)和蛋白质水平的表达模式。使用免疫组织学和核染色评估了Mcl - 1和Bax在耳蜗感觉上皮中的表达分布。 老年耳蜗的ABR阈值显著升高。这种变化伴随着老年个体中Mcl - 1在mRNA和蛋白质水平的表达以及Mcl - 1/Bax基因表达水平比例的显著降低。重要的是,Mcl - 1和Bax表达的变化在空间上与出现退化迹象的感觉细胞相关。
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.
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