Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells.,Acta Pharmacologica Sinica

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Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2020-03-02 , DOI: 10.1038/s41401-020-0378-6
Ya-Jie Xiong ₁ , Yun-Zhen Song ₁ , Ying Zhu ₂ , Wen-Qing Zuo ₁ , Yi-Fan Zhao ₁ , Xiao Shen ₁ , Wen-Juan Wang ₁ , Ya-Li Liu ₁ , Jun-Chao Wu ₁ , Zhong-Qin Liang ₁

Affiliation

Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway.

中文翻译：

奥氮平对鱼藤酮诱导的PC12细胞毒性的神经保护作用。

奥氮平是一种抗精神病药物，由于其锥体束外症状的发生率较低，因此用于治疗精神分裂症患者。先前的研究表明，奥氮平可激活AMP激活的蛋白激酶（AMPK），并诱导SH-SY5Y细胞系自噬。在这项研究中，我们调查了奥氮平是否能防御鱼藤酮诱导的PC12细胞神经毒性。我们表明，用奥氮平治疗可在PC12细胞中以剂量和时间依赖性方式增加AMPK的磷酸化。另外，奥氮平激活自噬并增加自噬泡。此外，奥氮平预处理可以保护PC12细胞免受鱼藤酮诱导的细胞凋亡。此外，奥氮平预处理可以抑制鱼藤酮诱导的线粒体去极化作用，从而保护细胞。此外，用特定的AMPK抑制剂化合物C或自噬抑制剂3-甲基腺嘌呤预处理可能会削弱奥氮平对鱼藤酮处理的PC12细胞的保护作用。总之，我们的结果首次表明奥氮平通过通过AMPK途径激活自噬来改善鱼藤酮诱导的损伤。

更新日期：2020-04-24

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