Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells
| Autor: | Yali Liu, Yajie Xiong, Wenjuan Wang, Yun-zhen Song, Zhongqin Liang, Xiao Shen, Yifan Zhao, Wenqing Zuo, Ying Zhu, Jun-Chao Wu |
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| Rok vydání: | 2020 |
| Předmět: |
AMPK
0301 basic medicine Olanzapine autophagy Cell Survival olanzapine AMP-Activated Protein Kinases Pharmacology Neuroprotection Article rotenone 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Extrapyramidal symptoms Tumor Cells Cultured medicine Animals Pharmacology (medical) Chemistry Autophagy Neurotoxicity PC12 cells General Medicine Rotenone medicine.disease Rats Neuroprotective Agents 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis neuroprotection medicine.symptom medicine.drug |
| Zdroj: | Acta Pharmacologica Sinica |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1038/s41401-020-0378-6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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