Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats.

Differential expression of apoptosis-related genes in the cochlea of noise-exposed rats.
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DOI:
10.1016/j.neuroscience.2009.03.072
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发表时间:
2009-07-07
期刊:
影响因子:
3.3
通讯作者:
Salvi, R.
Salvi, R.
中科院分区:
医学3区
文献类型:
--
作者:
Hu, B. H.;Cai, Q.;Manohar, S.;Jiang, H.;Ding, D.;Coling, D. E.;Zheng, G.;Salvi, R.

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强噪声暴露诱导耳蜗毛细胞凋亡。为了确定与噪声诱导的细胞凋亡相关的分子变化,我们使用定量实时PCR来评估84个细胞凋亡相关基因在耳蜗感觉上皮和外侧壁样本中的变化。Sprague道利大鼠暴露于115 dB SPL的连续噪声中2 h。暴露后4小时引起40-60 dB的阈值偏移,暴露后7天降至20-30 dB。这些功能变化与凋亡标志物相关,包括核浓缩和碎裂以及TUNEL染色。噪音暴露后,立即有12个基因下调,而只有一个基因(Traf 4)上调。暴露后4 h,8个基因上调; 3个(Tnrsf 1a、Tnfrsf 1b、Tnfrst 5)属于Tnfrsf家族,3个(Bir 3、Mcl 1和Prok 2)具有抗凋亡特性,1个(Gadd 45 a)是p53的靶点。暴露后7 d,所有上调的基因均恢复到噪声暴露前水平。有趣的是,正常对照耳蜗具有高组成水平的几个骨化相关基因。这些组成性表达的基因,连同诱导基因,可能参与耳蜗凋亡活性的诱导。
Exposure to intense noise induces apoptosis in hair cells in the cochlea. To identify the molecular changes associated with noise-induced apoptosis, we used quantitative real-time PCR to evaluate the changes in 84 apoptosis related genes in cochlear samples from the sensory epithelium and lateral wall. Sprague Dawley rats exposed to a continuous noise at 115 dB SPL for 2 h. The exposure caused a 40–60 dB threshold shift 4 h post-exposure that decreased to 20–30 dB 7 days post-exposure. These functional changes were associated with apoptotic markers including nuclear condensation and fragmentation and TUNEL staining. Immediately after the noise exposure, 12 genes were downregulated, whereas only one gene (Traf4) was upregulated. At 4 h post-exposure, 8 genes were upregulated; 3 (Tnrsf1a, Tnfrsf1b, Tnfrst5) belonged to the Tnfrsf family, 3 (Bir3, Mcl1 and Prok2) have anti-apoptotic properties and 1 (Gadd45a) is a target of p53. At 7 d post-exposure, all the upregulated genes returned to pre-noise levels. Interestingly, the normal control cochlea had high constitutive levels of several apoptosis-related genes. These constitutively expressed genes, together with the inducible genes, may participate in the induction of cochlear apoptotic activity.
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