Endoplasmic reticulum rather than mitochondria plays a major role in the neuronal apoptosis induced by polybrominated diphenyl ether-153
Authors: Jianying Bai
Xiaorong Yang
Zhihong Zhang
Hongmei Zhang
Ruifeng Liang
Xin Li
Qiao Niu
Lijun Chang
Tong Wang
Zemin Wang
Journal: Toxicology Letters (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: BDE-153; Endoplasmic reticulum; Mitochondria; Neuronal apoptosis.
Affiliations: Department of Radiological Health, General Hospital of Taiyuan Iron and Steel Company, Taiyuan, 030008, Shanxi, China., National Key Disciplines, Key Laboratory for Cellular Physiology of Ministry of Education, Department of Neurobiology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Environmental Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Environmental Health, Indiana University School of Public Health, Bloomington, IN, 47408, USA., Department of Health Statistics, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Occupational Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China., Department of Environmental Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China. Electronic address: .

Abstract:  Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons, however, the roles of mitochondria and endoplasmic reticulum (ER) remain unclear in the BDE-153-induced neuronal apoptosis. To this purpose, we observed the mitochondria and ER ultrastructure changes in the neuronal apoptosis in rats following BDE-153 treatment, detected the mitochondrial membrane potential (MMP), Ca2+-Mg2+-ATP enzyme activity, and the changes of mitochondria and ER apoptosis related molecules in rat cerebral cortex and in primary neurons following BDE-153 treatment. Results showed that compared to the control group, neuronal apoptosis was significantly increased in a dose-dependent manner in rat cerebral cortex and in primary neurons following BDE-153 treatment. In comparison with control, BDE-153 treatment induced remarkable ultrastructural changes in ER rather than in mitochondria, and the severity of ER damage was worse with the increasing BDE-153 dose. Meanwhile, ER apoptosis related molecules including caspase-12 (at mRNA level), cleaved caspase-12 (at protein level), and Tmem132a (at mRNA and protein levels) were significantly increased in the cerebral cortex in rats following BDE-153 treatment, while procaspase-12 protein was significantly decreased, comparing with control. In contrast, mitochondria apoptosis related molecules (MMP, Ca2+-Mg2+-ATP enzyme activity, cyt-C protein, caspase-3, 8, 9 mRNA, caspase-8, 9 enzyme activities) did not significantly changed in the cerebral cortex of rats or in primary neurons following BDE-153 treatment, except for the elevated caspase-3 mRNA and enzyme activity. Therefore, we conclude that BDE-153 induced neuronal apoptosis was dependent on p53, and mediated more by ER than mitochondria in the cerebral cortex of rats and in primary neurons. The findings suggest that ER is a potential sensitive target of BDE-153 neurotoxicity, providing a scientific evidence for the mechanism and intervention study on PBDE's neurotoxicity. 

Retracted: No

PubPeer comments:
 Figure5C and Figure5D ![file] , 
 #1 Thank you for your comment. We checked the raw data and found a wrong image of internal rederence was chosen and used. But it is doesn t alter the data result. We will be careful. , 
 #2 While you have acknowledged the error, there doesn t appear to be a correction yet. You may also wish to see other papers: https: pubpeer.com search?q=authors%3A Zhihong+Zhang (this is an author name search so perhaps some are by different authors with the same name). ,