Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells
Berberine attenuated the cytotoxicity induced by t-BHP via inhibiting oxidative stress and mitochondria dysfunction in PC-12 cells
复制标题
小檗碱通过抑制 PC-12 细胞中的氧化应激和线粒体功能障碍来减弱 t-BHP 诱导的细胞毒性
DOI：
10.1007/s10571-019-00756-7
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发表时间：
2020-05-01
影响因子：
4
通讯作者：
Hu, Aiping
中科院分区：
文献类型：
--
作者：
Li, Zhengmao;Jiang, Ting;Hu, Aiping
神经退行性疾病都有几个共同的特点，如参与氧化损伤和线粒体功能障碍的发病机制。由线粒体活性氧（ROS）的过度产生或抗氧化剂缺乏的损害诱导的氧化应激导致线粒体功能障碍和细胞死亡级联的启动。小檗碱（BBR）是一种传统中药，在中枢神经系统疾病中具有抗氧化应激和抗凋亡作用。然而，BBR调节线粒体自噬和保护氧化应激下线粒体功能的机制尚不清楚。在本研究中，我们评估了BBR对叔丁基过氧化氢（t-BHP）诱导的细胞毒性的有益作用。此外，我们探讨了BBR在氧化应激下对PC-12细胞线粒体功能和线粒体自噬的保护作用。我们的研究结果表明，BBR有效地抑制t-BHP诱导的细胞凋亡，这与减少乳酸脱氢酶（LDH）和ROS过量产生的泄漏。此外，BBR显着抑制细胞色素c的表达，上调Bcl-2/Bax的比例，并改善线粒体功能障碍，通过优化线粒体膜电位（Δ psi m）的状态和ATP的生产。此外，BBR还能降低自噬特异性标志物LC 3、SQTM 1/p62的表达，维持溶酶体正常功能，包括恢复上游信号通路AKT和mTOR磷酸化水平。总之，这些结果表明，BBR通过抑制ROS水平，线粒体功能障碍和线粒体自噬通过PI 3 K/AKT/mTOR信号通路保护PC-12细胞免受氧化损伤，这表明氧化应激和神经毒性损伤的潜在治疗策略。
Neurodegenerative diseases all share several common features such as involvement of oxidative damage and mitochondrial dysfunction in pathogenesis. Oxidative stress induced by overproduction of mitochondrial reactive oxygen species (ROS) or impairment of the antioxidant deficiency results in mitochondrial dysfunction and initiation of the cell death cascade. Berberine (BBR), a traditional Chinese medicine, has been reported to exert anti-oxidative stress and anti-apoptosis effect in CNS diseases. However, the mechanism of BBR on regulating mitophagy and protecting mitochondrial function under oxidative stress remains unclear. In present study, we evaluated the beneficial effects of BBR on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity. Furthermore, we explored the protective role of BBR in mitochondrial function and mitophagy under oxidative stress in PC-12 cells. Our results demonstrated that BBR effectively inhibited t-BHP-induced apoptosis which is associated with the decreased leakage of lactate dehydrogenase (LDH) and ROS overproduction. Moreover, BBR significantly suppressed cytochrome c expression, upregulated the ratio of Bcl-2/Bax, and ameliorated mitochondrial dysfunction by optimizing mitochondria membrane potential (Delta psi m) status and ATP production. In addition, BBR reduced the expression of autophagy-specific marker LC3, SQTM1/p62, and maintained lysosome normal function which involved the restoration of upstream signaling pathway AKT and mTOR phosphorylation level. Collectively, these findings suggested that BBR protects PC-12 cells from oxidative injury through inhibiting ROS level, mitochondria dysfunction, and mitophagy via PI3K/AKT/mTOR signaling pathways, which suggest a potential therapeutic strategy for oxidative stress and neurotoxic damages.