PINK1 protects against oxidative stress induced senescence of human nucleus pulposus cells via regulating mitophagy
PINK1 protects against oxidative stress induced senescence of human nucleus pulposus cells via regulating mitophagy
复制标题
PINK1通过调节线粒体自噬防止氧化应激诱导的人髓核细胞衰老
DOI：
10.1016/j.bbrc.2018.06.031
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发表时间：
2018-10-02
影响因子：
3.1
通讯作者：
Guo, Xiuming
中科院分区：
文献类型：
--
作者：
Wang, Yiyang;Shen, Jieliang;Guo, Xiuming
椎间盘退变（IDD）与衰老密切相关，而线粒体功能障碍是衰老的常见特征，导致细胞衰老。磷酸酶和张力蛋白同源物 (PTEN) 诱导的推定激酶蛋白 1 (PINK1) 是一种线粒体靶向丝氨酸/苏氨酸激酶，通过激活 PINK1/Parkin 介导的线粒体自噬，通过线粒体质量控制发挥针对线粒体功能障碍的保护作用。本研究旨在探讨 PINK1 对线粒体功能障碍和人髓核细胞 (NPC) 衰老的保护作用。我们发现150 μM H2O2 在亚致死氧化应激下可诱导线粒体功能障碍和鼻咽癌衰老。此外，氧化应激下PINK1的下调往往会加剧鼻咽癌的衰老。因此，对 NPC 中的线粒体自噬进行了评估，以进一步揭示其潜在机制。结果表明，亚致死氧化应激诱导 NPC 线粒体功能障碍和线粒体自噬。此外，利用靶向 PINK1 的短发夹 RNA (PINK1-shRNA) 来耗尽 PINK1 会损害线粒体自噬，并加剧氧化应激下的 NPC 衰老。总之，这些结果表明PINK1在清除受损线粒体和减轻氧化应激下细胞衰老方面发挥了保护作用，其机制与调节线粒体自噬有关。这些发现可能有助于更好地理解 IDD 的病理机制和 IDD 治疗的潜在治疗方法。 (C) 2018 年由爱思唯尔公司出版
Intervertebral disc degeneration (IDD) is closely related with aging, whereas mitochondrial dysfunction is a common feature of aging in which results cell senescence. Phosphatase and tensin homolog (PTEN)induced putative kinase protein 1 (PINK1) is a mitochondrial-targeted serine/threonine kinase, which plays a protective role against mitochondrial dysfunction with mitochondrial quality control by activating PINK1/Parkin mediated mitophagy. This study aimed to investigate the protective role of PINK1 against mitochondrial dysfunction and human nucleus pulposus cell (NPC) senescence. We found that mitochondrial dysfunction and NPC senescence could be induced under sublethal oxidative stress by 150 mu M H2O2. Moreover, down-regulation of PINK1 tended to aggravate NPC senescence under oxidative stress. Therefore, mitophagy was evaluated in NPCs to further reveal the underlying mechanism. Results showed that sublethal oxidative stress induced mitochondria dysfunction and mitophagy in NPCs. Furthermore, depletion of PINK1 utilizing short hairpin RNA targeting PINK1 (PINK1-shRNA) impaired mitophagy, and exasperated NPC senescence under oxidative stress. In summary, these results suggested that PINK1 played as a protective role in clearance of damaged mitochondrial and alleviating cell senescence under oxidative stress, whose mechanism is associated with regulating mitophagy. These findings may provide a better understanding in pathomechanism of IDD and potential therapeutic approaches for IDD treatment. (C) 2018 Published by Elsevier Inc.