Heat shock factor 1-deficient mice exhibit decreased recovery of hearing following noise overstimulation
Heat shock factor 1-deficient mice exhibit decreased recovery of hearing following noise overstimulation
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DOI：
10.1002/jnr.20417
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发表时间：
2005-08-15
影响因子：
4.2
通讯作者：
Altschuler, RA
中科院分区：
文献类型：
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作者：
Fairfield, DA;Lomax, MI;Altschuler, RA
热休克蛋白（Hsps）能够在应激反应中提高细胞存活率。热休克因子1（Hsf1）是调节应激诱导的热休克蛋白表达的主要转录因子。我们先前已证实热休克因子1存在于啮齿动物的耳蜗中，并且还证明已知能使耳蜗对噪声损伤产生预处理作用的热休克会导致啮齿动物耳蜗中热休克因子1的激活。在本研究中，我们使用热休克因子1缺陷型（Hsf1（-/-））小鼠模型来确定消除依赖于热休克因子1的应激通路是否会影响中度强度噪声导致的听力损失和/或听力恢复。热休克因子1（-/-）小鼠及其正常同窝小鼠（Hsf1（+/+））暴露于98分贝、宽带（2 - 20千赫兹）的噪声中2小时，并且在噪声暴露后3小时、3天和2周时在三个频率（4千赫兹、12千赫兹和20千赫兹）测量听性脑干反应阈值。热休克因子1（-/-）小鼠比热休克因子1（+/+）小鼠有更严重的听力损失，在噪声暴露2周后所测试的所有频率上都观察到恢复方面的显著差异。在噪声暴露后，热休克因子1（-/-）小鼠中外毛细胞损失也有所增加。这些研究为热休克因子1在噪声过度刺激后的耳蜗保护、恢复和/或修复中的重要性提供了证据。（c）2005威利 - 利斯公司
Heat shock proteins (Hsps) can enhance cell survival in response to stress. Heat shock factor 1 (Hsf1) is the major transcription factor that regulates stress-inducible Hsp expression. We previously demonstrated the presence of Hsf1 in the rodent cochlea and also demonstrated that a heat shock known to precondition the cochlea against noise trauma results in Hsf1 activation in the rodent cochlea. In the present study, we used an Hsf1-deficient (Hsf1(-/-)) mouse model to determine whether eliminating the Hsf1-dependent stress pathway would influence hearing loss and/or recovery from a moderate-intensity noise. Hsf1(-/-) mice and their normal littermates (Hsf1(+/+)) were exposed to a 98-dB, broadband (2-20 kHz) noise for 2 hr, and auditory brainstem response thresholds were measured at three frequencies (4, 12, and 20 kHz) 3 hr, 3 days, and 2 weeks after noise. Hsf1(-/-) mice had greater hearing loss than Hsf1(+/+) mice, with significant differences in recovery observed at all frequencies tested by 2 weeks after noise. Increased outer hair cell loss was also observed in Hsf1(-/-) mice following noise. These studies provide evidence for the importance of Hsf1 in cochlear protection, recovery, and/or repair following noise overstimulation. (c) 2005 Wiley-Liss, Inc.