Waldmann Dominique, Lu Yu, Cortada Maurizio, Bodmer Daniel, Levano Huaman Soledad
University of Basel Hospital, Department of Biomedicine, Basel, Switzerland.
University of Basel Hospital, Department of Biomedicine, Basel, Switzerland; University of Basel Hospital, Clinic for Otolaryngology, Head and Neck Surgery, Basel, Switzerland.
Biochem Biophys Res Commun. 2023 Oct 20;678:115-121. doi: 10.1016/j.bbrc.2023.08.033. Epub 2023 Aug 17.
Loss of hair cells can lead to irreversible sensorineural hearing loss. Therefore, hair cell preservation is critical for hearing. Mitochondrial derived peptides (MDPs) are bioactive peptides and prominent members of this family are humanin (HN) and the mitochondrial-open-reading frame of the twelve S c (MOTS-c). The protective roles of HN and MOTS-c in age-related diseases and in various tissues exposed to cellular stresses have been demonstrated. The involvement of MDPs in the inner ear remains to be investigated. Therefore, we determined the expression of rattin, the homolog of humanin, in inner ear tissues. Then, we found that HN and MOTS-c showed a significant protective effect on hair cells in organ of Corti explants exposed to gentamicin. Treatment with HN decreased gentamicin-induced phosphorylation of AKT, whereas treatment with MOTS-c increased phosphorylation of AMPKα in explants. Our data indicate that MDPs exert a protective function in gentamicin-induced hair cell damage. Therefore, MDPs may contribute to design new preventive strategies against hearing loss.
毛细胞的丧失会导致不可逆的感音神经性听力损失。因此，毛细胞的保存对听力至关重要。线粒体衍生肽（MDPs）是生物活性肽，该家族的重要成员有人源蛋白（HN）和十二S c的线粒体开放阅读框（MOTS-c）。HN和MOTS-c在与年龄相关的疾病以及暴露于细胞应激的各种组织中的保护作用已得到证实。MDPs在内耳中的作用仍有待研究。因此，我们测定了人源蛋白的同源物大鼠蛋白在内耳组织中的表达。然后，我们发现HN和MOTS-c对暴露于庆大霉素的柯蒂氏器外植体中的毛细胞具有显著的保护作用。用HN处理可降低庆大霉素诱导的AKT磷酸化，而用MOTS-c处理可增加外植体中AMPKα的磷酸化。我们的数据表明，MDPs在庆大霉素诱导的毛细胞损伤中发挥保护作用。因此，MDPs可能有助于设计预防听力损失的新策略。
