Kalvani Zahra, Kamunde Collins, Stevens Don, van den Heuvel Michael R
Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada.
Atlantic Veterinary College, Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada.
Environ Toxicol Pharmacol. 2024 Apr;107:104386. doi: 10.1016/j.etap.2024.104386. Epub 2024 Feb 9.
The naphthenic acid fraction compound (NAFC), 3,5-dimethyladamantane-1-acetic acid, was tested for its ability to uncouple mitochondrial oxidative phosphorylation. Mitochondria isolated from rainbow trout (Oncorhynchus mykiss) liver were exposed to 3,5-dimethyladamantane-1-acetic acid in state 3 and 4 respiration, and mitochondrial membrane potential were quantified. Electron transport chain (ETC) protein complexes were isolated using pharmacological agents and inhibitors, and their activities measured. The NAFC compound completely inhibited states 3 and 4 respiration with an IC50 of 0.77 and 1.01 mM, respectively. The NAFC compound partially uncoupled mitochondrial membrane potential in state 3 and 4 respiration with an IC50 of 2.19 and 1.73 mM, respectively. The NAFC impaired the activities of ETC protein complexes with a 9.5-fold range in sensitivity. The relative inhibitory effect of the ETC protein complexes to NAFC was CIV≥CI>CIII>CII. The impairment of mitochondrial oxidative phosphorylation by adamantane 3,5-dimethyladamantane-1-acetic acid is mediated via its inhibition of ETC protein complexes.
对环烷酸馏分化合物（NAFC），即3,5 - 二甲基金刚烷 - 1 - 乙酸，进行了其解偶联线粒体氧化磷酸化能力的测试。从虹鳟（Oncorhynchus mykiss）肝脏分离的线粒体在呼吸状态3和4下暴露于3,5 - 二甲基金刚烷 - 1 - 乙酸，并对线粒体膜电位进行了定量。使用药理试剂和抑制剂分离电子传递链（ETC）蛋白复合物，并测量其活性。NAFC化合物完全抑制呼吸状态3和4，其IC50分别为0.77和1.01 mM。NAFC化合物在呼吸状态3和4下部分解偶联线粒体膜电位，其IC50分别为2.19和1.73 mM。NAFC损害ETC蛋白复合物的活性，敏感性范围为9.5倍。ETC蛋白复合物对NAFC的相对抑制作用为CIV≥CI>CIII>CII。金刚烷3,5 - 二甲基金刚烷 - 1 - 乙酸对线粒体氧化磷酸化的损害是通过其对ETC蛋白复合物的抑制介导的。
