Ototoxicity-induced loss of hearing and inner hair cells is attenuated by HSP70 gene transfer.
Ototoxicity-induced loss of hearing and inner hair cells is attenuated by HSP70 gene transfer.
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DOI：
10.1038/mtm.2015.19
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发表时间：
2015
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影响因子：
--
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感觉神经性耳聋最常见的原因是毛细胞死亡。热休克蛋白(HSPs)是参与蛋白质折叠、靶向和降解的分子伴侣。热休克蛋白的表达随着各种环境压力的增加而增加，以保护细胞免受损伤。在这里，我们测试了病毒介导的HSP70过表达是否可以在豚鼠身上保护HCS和听力免受严重的耳毒性(卡那霉素和速尿)的影响。实验动物注射腺病毒HSP70-mCherry(Ad.HSP70-mCherry)，对照组注射腺病毒-mCherry，4天后进行耳毒性实验。用听性脑干反应测量受辱前、受辱后14天、处死动物之前的听力阈值。EPI-荧光免疫细胞化学显示，注射Ad.HSP70-mCherry后，Corti器无感觉细胞内出现mCherry荧光。耳毒性侮辱消除了对照(注射了腺病毒mCherry)耳和对侧(未注射)耳的大部分耳蜗外HCs和内HCs。Ad.HSP70-mCherry注射耳与对照耳和对侧耳相比，表现出显著的内HCS保存，但外HCS不受保护。注射Ad.HSP70-mCherry组的听性脑干反应阈值明显好于对照组和对侧耳。我们的数据显示，HSP70的增加可能代表了一种减少耳毒性内源性HC丢失的潜在治疗方法。
The most common reason for sensorineural deafness is death of hair cells (HCs). Heat shock proteins (HSPs) are molecular chaperones that participate in folding, targeting, and degrading proteins. HSP expression is increased in response to various environmental stresses to protect cells from damage. Here, we tested whether viral-mediated overexpression of HSP70 can protect HCs and hearing from severe ototoxicity (kanamycin and furosemide) in guinea pigs. Adenovirus-HSP70 mCherry (Ad.HSP70-mCherry) was injected to experimental animals and adenovirus-mCherry to controls, 4 days before the ototoxic insult. Hearing thresholds were measured by auditory brainstem response before the insult and again before sacrificing the animals, 14 days after the insult. Epi-fluorescence immunocytochemistry showed that injection of Ad.HSP70-mCherry resulted in mCherry fluorescence in nonsensory cells of the organ of Corti. The ototoxic insult eliminated both outer HCs and inner HCs throughout most of the cochlea of control (adenovirus-mCherry-injected) ears and contralateral (uninjected) ears. Ad.HSP70-mCherry-injected ears exhibited a significant preservation of inner HCs compared to control and contralateral ears, but outer HCs were not protected. Auditory brainstem response thresholds were significantly better in Ad.HSP70-mCherry-injected ears than in control and contralateral ears. Our data show that HSP70 augmentation may represent a potential therapy attenuating ototoxic inner HC loss.
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影响因子：
5.3
作者：
Lahne, Manuela;Gale, Jonathan E.
通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1007/s10162-006-0043-x
发表时间：
2006-09-01
影响因子：
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通讯作者：
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影响因子：
2.8
作者：
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通讯作者：
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