Decabromodiphenyl ether initiates mitochondria-dependent apoptosis by disrupting calcium homeostasis in mice livers,Chemosphere

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Decabromodiphenyl ether initiates mitochondria-dependent apoptosis by disrupting calcium homeostasis in mice livers
Chemosphere ( IF 8.1 ) Pub Date : 2021-11-05 , DOI: 10.1016/j.chemosphere.2021.132767
Siyan Che ₁ , Sunni Chen ₁ , Shiqi Li ₁ , Zheng Ruan ₁

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Decabromodiphenyl ether (BDE-209) tends to accumulate in lipid-rich tissues and targets the liver since its high lipophilicity. This study aimed to investigate the effects of BDE-209 on mouse liver and reveal the underlying toxicological mechanisms. Here we firstly confirmed that treatment of BDE-209 could lead to an imbalance of redox and promote apoptosis with a mitochondria-dependent manner in mice livers. Next, the transmission electron microscope (TEM) image revealed BDE-209 induced changes in mitochondrial morphology and increased endoplasmic reticulum (ER) - mitochondrial contact. ER stress was involved in the apoptosis process, which was displayed by the enhancive ER stress makers . Finally, from the increased abundance of cellular pivotal Ca2+ signals transducer CaM, activating Ca2+ release channel Sig-1R and IP3R1, and the stronger fluorescence density of mitochondria-specifically Ca2+ labeled probe Rhod-2 in vitro, we summarized that there was overloaded mitochondrial Ca2+ in hepatocytes of BDE-209 treated mice. In conclusion, these results partly illustrated evidence to reveal a potential mechanism of BDE-209-induced hepatoxicity, where oxidative stress-induced-ER stress led to the over-release of Ca2+, followed by the overloaded mitochondrial Ca2+, and cell apoptosis initiated. Our findings provided a theoretical basis for further studying.

中文翻译：

十溴二苯醚通过破坏小鼠肝脏的钙稳态来启动线粒体依赖性细胞凋亡

十溴二苯醚（BDE-209）由于其高亲脂性，倾向于在富含脂质的组织中积累并靶向肝脏。本研究旨在探讨 BDE-209 对小鼠肝脏的影响并揭示潜在的毒理学机制。在这里，我们首先证实 BDE-209 的治疗可导致小鼠肝脏氧化还原失衡并以线粒体依赖性方式促进细胞凋亡。接下来，透射电子显微镜（TEM）图像显示 BDE-209 诱导了线粒体形态的变化和内质网（ER） - 线粒体接触的增加。ER 应激参与细胞凋亡过程，这由增强的 ER 应激制造者显示。最后，从细胞关键 Ca2 + 信号换能器的丰度增加，激活 Ca2 + 释放通道 Sig-1R 和 IP3R1，以及线粒体特异性 Ca2 + 标记探针 Rhod-2 在体外的更强荧光密度，我们总结了 BDE-209 处理小鼠的肝细胞中存在超负荷的线粒体 Ca2 +。总之，这些结果部分说明了揭示 BDE-209 诱导肝毒性的潜在机制的证据，其中氧化应激诱导的 ER 应激导致 Ca2+ 过度释放，然后是线粒体超负荷 Ca2+，细胞凋亡开始。我们的研究结果为进一步研究提供了理论基础。

更新日期：2021-11-05

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