Noise induced changes in the expression of p38/MAPK signaling proteins in the sensory epithelium of the inner ear.
Noise induced changes in the expression of p38/MAPK signaling proteins in the sensory epithelium of the inner ear.
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DOI：
10.1016/j.jprot.2011.08.007
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发表时间：
2011-12-21
影响因子：
3.3
通讯作者：
Salvi R
中科院分区：
文献类型：
--
作者：
Jamesdaniel S;Hu B;Kermany MH;Jiang H;Ding D;Coling D;Salvi R
噪音暴露是听力损失的主要原因。研究蛋白质参与的经典方法为理解介导听力损失和损伤修复的信号通路提供了基础，但不适用于研究在噪音创伤期间可能增加或减少的大型蛋白质网络。为了解决这个问题，使用抗体微阵列来量化龙猫耳蜗三个不同区域在 112 dB SPL 的 0.5-8 kHz 噪声带暴露 2 小时后 2 小时内蛋白质表达的早期变化。噪声暴露在暴露后 2 小时造成显着的功能损伤，但仅部分恢复。畸变产物耳声发射在暴露后2小时消除，但在暴露后4周时，耳声发射仍然存在，但仍然严重抑制。暴露后 4 周获得的耳蜗图显示，与噪声频谱中的频率相对应的耳蜗基底 60% 中的外毛细胞显着损失。对早期（暴露后 2 小时）噪声引起的蛋白质组变化的比较分析表明，感觉上皮、侧壁和轴轴对噪声的生物反应不同。使用“The Database for Annotation, Visualization and Integrated Discovery 2008”（DAVID - http://david.abcc.ncifcrf.gov）对耳蜗蛋白质谱进行生物信息分析，揭示了感觉上皮和蜗轴细胞死亡过程的启动。感觉上皮中 Fas 和 FAK 和 p38/MAPK 磷酸化的增加表明，细胞膜上噪声诱导的应激信号通过 Fas 和粘着斑信号通过 p38/MAPK 信号通路传递到细胞核。免疫印迹和微阵列中下游核蛋白 E2F3 和 WSTF 的上调及其在外毛细胞中的免疫定位支持 p38/MAPK 信号传导在噪声引起的听力损失机制中的关键作用。
Noise exposure is a major cause of hearing loss. Classical methods of studying protein involvement have provided a basis for understanding signaling pathways that mediate hearing loss and damage repair but do not lend themselves to studying large networks of proteins that are likely to increase or decrease during noise trauma. To address this issue, antibody microarrays were used to quantify the very early changes in protein expression in three distinct regions of the chinchilla cochlea 2 h after exposure to a 0.5–8 kHz band of noise for 2 h at 112 dB SPL. The noise exposure caused significant functional impairment 2 h post-exposure which only partially recovered. Distortion product otoacoustic emissions were abolished 2 h after the exposure, but at 4 weeks post-exposure, otoacoustic emissions were present, but still greatly depressed. Cochleograms obtained 4 weeks post-exposure demonstrated significant loss of outer hair cells in the basal 60% of the cochlea corresponding to frequencies in the noise spectrum. A comparative analysis of the very early (2 h post-exposure) noise-induced proteomic changes indicated that the sensory epithelium, lateral wall and modiolus differ in their biological response to noise. Bioinformatic analysis of the cochlear protein profile using “The Database for Annotation, Visualization and Integrated Discovery 2008” (DAVID - http://david.abcc.ncifcrf.gov) revealed the initiation of the cell death process in sensory epithelium and modiolus. An increase in Fas and phosphorylation of FAK and p38/MAPK in the sensory epithelium suggest that noise-induced stress signals at the cell membrane are transmitted to the nucleus by Fas and focal adhesion signaling through the p38/MAPK signaling pathway. Up-regulation of downstream nuclear proteins E2F3 and WSTF in immunoblots and microarrays along with their immunolocalization in the outer hair cells supported the pivotal role of p38/MAPK signaling in the mechanism underlying noise-induced hearing loss.
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影响因子：
2.6
作者：
Haley B;Paunesku T;Protić M;Woloschak GE
通讯作者：
Woloschak GE
影响因子：
30.8
作者：
Evans, AL;Müller, U
通讯作者：
Müller, U
影响因子：
6.5
作者：
Dusek, Rachel L.;Godsel, Lisa M.;Green, Kathleen J.
通讯作者：
Green, Kathleen J.
影响因子：
5.3
作者：
Bozkulak, Esra Cagavi;Weinmaster, Gerry
通讯作者：
Weinmaster, Gerry
DOI：
10.1023/a:1018523827852
发表时间：
1997-02-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Coling, DE;Espreafico, EM;Kachar, B
通讯作者：
Kachar, B