Ahn Changhwan, Jeong SunHwa, Jeung Eui-Bae
Laboratory of Veterinary Physiology, College of Veterinary Medicine, Jeju National University, Jeju, 63243 Republic of Korea.
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644 Republic of Korea.
Toxicol Res. 2022 Dec 13;39(2):239-249. doi: 10.1007/s43188-022-00161-1. eCollection 2023 Apr.
Mitochondria need to use considerable energy for the intracellular organelles that produce ATP. They are abundant in the cells of organs, such as muscles, liver, and kidneys. The heart, which requires a lot of energy, is also rich in mitochondria. Mitochondrial damage can induce cell death. Doxorubicin, acetaminophen, valproic acid, amiodarone, and hydroxytamoxifen are representative substances that induce mitochondrial damage. On the other hand, the effects of this substance on the progress of cardiomyocyte-differentiating stem cells have not been investigated. Therefore, a 3D cultured embryonic body toxicity test was performed. The results confirmed that the cytotoxic effects on cardiomyocytes were due to mitochondrial damage in the stage of cardiomyocyte differentiation. After drug treatment, the cells were raised in the embryoid body state for four days to obtain the ID values, and the levels of mRNA expression associated with the mitochondrial complex were examined. The mitochondrial DNA copy numbers were also compared to prove that the substance affects the number of mitochondria in EB-state cardiomyocytes.
The online version contains supplementary material available at 10.1007/s43188-022-00161-1.
线粒体作为产生三磷酸腺苷(ATP)的细胞内细胞器,需要消耗大量能量。它们在肌肉、肝脏和肾脏等器官的细胞中含量丰富。心脏需要大量能量,因此线粒体也很丰富。线粒体损伤可诱导细胞死亡。阿霉素、对乙酰氨基酚、丙戊酸、胺碘酮和羟基他莫昔芬是诱导线粒体损伤的代表性物质。另一方面,该物质对心肌细胞分化干细胞进程的影响尚未得到研究。因此,进行了三维培养胚状体毒性试验。结果证实,在心肌细胞分化阶段,对心肌细胞的细胞毒性作用是由线粒体损伤引起的。药物处理后,将细胞在胚状体状态下培养四天以获得ID值,并检测与线粒体复合体相关的mRNA表达水平。还比较了线粒体DNA拷贝数,以证明该物质影响EB状态心肌细胞中的线粒体数量。
在线版本包含可在10.1007/s43188-022-00161-1获取的补充材料。