Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway.
Adjudin protects rodent cochlear hair cells against gentamicin ototoxicity via the SIRT3-ROS pathway.
复制标题
Adjudin 通过 SIRT3-ROS 通路保护啮齿动物耳蜗毛细胞免受庆大霉素耳毒性
DOI：
10.1038/srep08181
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发表时间：
2015-02-02
影响因子：
4.6
通讯作者：
Gao WQ
中科院分区：
文献类型：
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作者：
Quan Y;Xia L;Shao J;Yin S;Cheng CY;Xia W;Gao WQ
由毛细胞退化引起的听力损失是一种影响全世界数百万人的常见疾病。克服哺乳动物明显不可逆的毛细胞损失的策略对听力保护至关重要。在这里，我们报道，通过使用一个完善的庆大霉素诱导的毛细胞脱落的体外模型，裁决，一个多功能小分子药物，保护耳蜗毛细胞免受庆大霉素损伤。免疫组织化学、Western blotting和定量RT-PCR分析显示，裁决素通过上调Sirt3水平发挥耳蜗保护作用，Sirt3是Sirtuin家族成员，位于线粒体，调节耳蜗细胞活性氧（ROS）的产生，抑制庆大霉素诱导的ROS的产生和凋亡细胞。Sirt3沉默实验证实Sirt3- ros信号轴至少部分介导了裁决素对庆大霉素的毛细胞保护作用。此外，在动物模型中也观察到了裁决素的耳保护作用。综上所述，这些发现确定了裁决蛋白是一种通过提高Sirt3水平来保护耳的新型小分子，Sirt3可能在保护毛细胞免受耳毒性损伤方面具有治疗价值。
Hearing loss resulting from hair cell degeneration is a common disease that affects millions of people worldwide. Strategies to overcome the apparent irreversible hair cell loss in mammals become paramount for hearing protection. Here we reported that, by using a well-established gentamicin-induced hair cell loss modelin vitro, adjudin, a multi-functional small molecule drug, protected cochlear hair cells from gentamicin damage. Immunohistochemistry, Western blotting and quantitative RT-PCR analyses revealed that adjudin exerted its otoprotective effects by up-regulating the level of Sirt3, a member of Sirtuin family protein located in mitochondria, which regulates reactive oxygen species (ROS) production in cochlear cells and inhibits the production of ROS and apoptotic cells induced by gentamicin. Sirt3 silencing experiments confirmed that Sirt3-ROS signaling axis mediated hair cell protection against gentamicin by adjudin, at least in part. Furthermore, adjudin's otoprotection effects were also observed in anin vivogentamicin-injured animal model. Taken together, these findings identify adjudin as a novel otoprotective small molecule via elevating Sirt3 levels and Sirt3 may be of therapeutic value in hair cell protection from ototoxic insults.
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影响因子：
16.2
作者：
Mizutari K;Fujioka M;Hosoya M;Bramhall N;Okano HJ;Okano H;Edge AS
通讯作者：
Edge AS
影响因子：
4.8
作者：
Setsukinai, K;Urano, Y;Nagano, T
通讯作者：
Nagano, T
影响因子：
--
作者：
Okano, Takayuki;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
影响因子：
12.8
作者：
Lee, Jeong-Han;Park, Channy;Kim, Se-Jin;Kim, Hyung-Jin;Oh, Gi-Su;Shen, AiHua;So, Hong-Seob;Park, Raekil
通讯作者：
Park, Raekil
影响因子：
3.3
作者：
通讯作者：
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