Alqudah Safa, Chertoff Mark, Durham Dianne, Moskovitz Jackob, Staecker Hinrich, Peppi Marcello
Department of Hearing and Speech, School of Health Professions, University of Kansas Medical Center, Kansas City, Kansas, USA.
Division of Hearing and Speech<bold>,</bold> Department of Rehabilitation Sciences, School of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan.
Audiol Neurootol. 2018;23(1):20-31. doi: 10.1159/000488276. Epub 2018 Jun 21.
Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy.
蛋氨酸亚砜还原酶（MsrA和MsrB）可保护蛋白质的生物活性免受蛋氨酸残基氧化修饰的影响，对于预防神经退行性疾病的病理效应具有重要意义。在本研究中，我们对MsrA基因敲除小鼠的听觉表型进行了特征描述。与野生型小鼠相比，年轻的MsrA基因敲除小鼠在听觉脑干反应和畸变产物耳声发射方面表现出较小的高频阈值升高，而在老年MsrA基因敲除小鼠中这种情况逐渐恶化。MsrA基因敲除小鼠在幼年和老年时对噪声的敏感性均增加，这表明MsrA是保护耳蜗免受声学损伤机制的一部分。声学刺激后耳蜗中的MsrA mRNA增加。最后，MsrB1 mRNA的表达在6个月大时受损，但在较年轻的MsrA基因敲除小鼠中未受损（与对照组相比）。耳蜗中MsrA作为早期听力损失和声损伤的保护性介质的鉴定，扩展了我们对可能诱导声损伤保护的途径的理解，并促进了关于如何通过基于Msr的疗法预防噪声暴露损伤效应的进一步研究。
