Decabromodiphenyl ether initiates mitochondria-dependent apoptosis by disrupting calcium homeostasis in mice livers
| Autor: | Shiqi Li, Siyan Che, Sunni Chen, Zheng Ruan |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Environmental Engineering
Health Toxicology and Mutagenesis Apoptosis Oxidative phosphorylation Mitochondrion medicine.disease_cause Mice Halogenated Diphenyl Ethers medicine Animals Homeostasis Environmental Chemistry Calcium metabolism Chemistry Endoplasmic reticulum Public Health Environmental and Occupational Health General Medicine General Chemistry Endoplasmic Reticulum Stress Pollution In vitro Mitochondria Cell biology Liver Unfolded protein response Calcium Oxidative stress |
| Zdroj: | Chemosphere. 291:132767 |
| ISSN: | 0045-6535 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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