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

• DOI: 10.1016/j.tox.2022.153275
• Publication Date: 2022-07-27T00:24:02Z
• Authors: Sisi Lei; Yuchao Feng; Peiying Huang; BoJun Chen; Kun Bao; Qihua Wu; Haobo Zhang; Xiaoyan Huang
• Keywords: PINK1

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