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Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells

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收录情况： ◇ SCIE

作者：
Lei Sisi[1,3] * ; Feng Yuchao[2,3] ; Huang Peiying[1,3] ; Chen BoJun[2,3] ; Bao Kun[2] ; Wu Qihua[1,3] ; Zhang Haobo[1,3] ; Huang Xiaoyan[2,3,*1] ;
机构： [1]The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China [2]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China [3]Guangdong Provincial Key Laboratory of Research on Emergency in Traditional Chinese Medicine, Clinical Research Team of Prevention and Treatment of Cardiac Emergencies with Traditional Chinese Medicine, Guangzhou 510120, China
出处：
DOI： 10.1016/j.tox.2022.153275
ISSN：

摘要：
Shenmai injection (SMI) is a patented traditional Chinese medicine that is extracted from Panax ginseng and Ophiopogon japonicus and is commonly used to treat cardiovascular diseases and tumors. The O. japonicus extract Ophiopogonin D' (OPD') is highly cardiotoxic. Mitochondria are central to OPD'-induced cardiotoxicity, although the precise mechanisms remain unclear. Excessive mitophagy activation and mitochondrial dysfunction lead to apoptosis, and the PTEN-induced kinase 1(PINK1)/Parkin pathway is critical in regulating mitophagy and mitochondrial function. We investigated the role of the PINK1/Parkin pathway in OPD'-induced mitochondrial damage and cardiotoxicity in AC16 cells. Concentrations of 2μM OPD' and above inhibited cardiomyocyte viability and increased lactate dehydrogenase (LDH) release in a concentration- and time-dependent manner. OPD' was toxic to cells and mitochondria and increased the rate of apoptosis, triggering pyknosis, decreasing mitochondrial membrane potential (MMP), and decreasing the protein expression of the biogenesis regulator peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α). The increased ratio of microtubule-associated proteins 1A/1B light chain 3B (LC3-II/LC3-I) in mitochondria indicated that OPD' induced mitophagy. OPD' significantly induced oxidative stress and apoptosis, including increased reactive oxygen species (ROS) generation and decreased nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1(HO-1), and B-cell lymphoma 2 (Bcl-2) protein expression. OPD' activated the PINK1/Parkin pathway and promoted PINK1/Parkin translocation to mitochondria. Inhibiting mitophagy attenuated OPD'-induced PINK1/Parkin pathway activation and preserved mitochondrial biogenesis, consequently mitigating OPD'-induced mitochondrial dysfunction and apoptosis. These findings suggest that OPD'-induced cardiomyocyte mitophagy and mitochondrial damage are at least partially mediated by dysregulation of the PINK1/Parkin pathway.Copyright © 2022. Published by Elsevier B.V.

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外文
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中科院(CAS)分区：
出版当年[2021]版：
大类 | 3 区 医学
小类 | 2 区 药学 2 区 毒理学
最新[2025]版：
大类 | 3 区 医学
小类 | 2 区 药学 2 区 毒理学
JCR分区：
出版当年[2020]版：
Q2 TOXICOLOGY Q2 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY Q1 TOXICOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China [3]Guangdong Provincial Key Laboratory of Research on Emergency in Traditional Chinese Medicine, Clinical Research Team of Prevention and Treatment of Cardiac Emergencies with Traditional Chinese Medicine, Guangzhou 510120, China
通讯作者：
通讯机构： [2]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China [3]Guangdong Provincial Key Laboratory of Research on Emergency in Traditional Chinese Medicine, Clinical Research Team of Prevention and Treatment of Cardiac Emergencies with Traditional Chinese Medicine, Guangzhou 510120, China [*1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 111 Dade Road, Guangzhou 510120, China.
推荐引用方式(GB/T 7714)：
Lei Sisi,Feng Yuchao,Huang Peiying,et al.Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells[J].TOXICOLOGY.2022,477:doi:10.1016/j.tox.2022.153275.
APA：
Lei Sisi,Feng Yuchao,Huang Peiying,Chen BoJun,Bao Kun...&Huang Xiaoyan.(2022).Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells.TOXICOLOGY,477,
MLA：
Lei Sisi,et al."Ophiopogonin D'-induced mitophagy and mitochondrial damage are associated with dysregulation of the PINK1/Parkin signaling pathway in AC16 cells".TOXICOLOGY 477.(2022)

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