Mitochondrial dynamics when mitochondrial toxic chemicals exposed in 3D cultured mouse embryonic stem cell.

IF 1.6 4区 医学 Q4 TOXICOLOGY
Toxicological Research Pub Date : 2022-12-13 eCollection Date: 2023-04-01 DOI:10.1007/s43188-022-00161-1
Changhwan Ahn, SunHwa Jeong, Eui-Bae Jeung
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引用次数: 0

Abstract

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 ID50 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.

Supplementary information: The online version contains supplementary material available at 10.1007/s43188-022-00161-1.

三维培养的小鼠胚胎干细胞暴露于线粒体有毒化学物质时的线粒体动力学。
线粒体是产生 ATP 的细胞内细胞器,需要消耗大量能量。它们大量存在于肌肉、肝脏和肾脏等器官的细胞中。需要大量能量的心脏也含有丰富的线粒体。线粒体损伤可导致细胞死亡。多柔比星、对乙酰氨基酚、丙戊酸、胺碘酮和羟氨嘧啶是诱导线粒体损伤的代表性物质。另一方面,这种物质对心肌细胞分化干细胞进展的影响尚未得到研究。因此,我们进行了三维培养胚胎体毒性试验。结果证实,对心肌细胞的细胞毒性作用是由心肌细胞分化阶段的线粒体损伤引起的。药物处理后,将细胞在类胚体状态下培养四天,以获得 ID50 值,并检测与线粒体复合物相关的 mRNA 表达水平。此外,还比较了线粒体 DNA 的拷贝数,以证明该物质会影响 EB 状态心肌细胞中线粒体的数量:在线版本包含补充材料,可查阅 10.1007/s43188-022-00161-1。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.20
自引率
4.30%
发文量
39
期刊介绍: Toxicological Research is the official journal of the Korean Society of Toxicology. The journal covers all areas of Toxicological Research of chemicals, drugs and environmental agents affecting human and animals, which in turn impact public health. The journal’s mission is to disseminate scientific and technical information on diverse areas of toxicological research. Contributions by toxicologists, molecular biologists, geneticists, biochemists, pharmacologists, clinical researchers and epidemiologists with a global view on public health through toxicological research are welcome. Emphasis will be given to articles providing an understanding of the toxicological mechanisms affecting animal, human and public health. In the case of research articles using natural extracts, detailed information with respect to the origin, extraction method, chemical profiles, and characterization of standard compounds to ensure the reproducible pharmacological activity should be provided.
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