Melatonin relieves 2,2,4,4-tetrabromodiphenyl ether (BDE-47)-induced apoptosis and mitochondrial dysfunction through the AMPK-Sirt1-PGC-1α axis in fish kidney cells (CIK)
Peixian Luan, Haoran Zhang, Xiaoming Chen, Zhu Feng Yue, Guo Hu, Jingzeng Cai, Ziwei Zhang
Abstract
Polybrominated diphenyl ethers (PBDEs) exist in aquatic environments with nephrotoxicity to non-target aquatic species. Melatonin (MT) exhibits an inhibitory effect of oxidative stress and apoptosis in various diseases. 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) is the main homolog of PBDE samples. Therefore, we investigated the toxic mechanism of BDE-47 and the alleviation effect of MT, the ctenopharyngodon idellus kidney (CIK) cells were treated with BDE-47 (100 μM) and/or MT (60 μM) for 24 h. Firstly, BDE-47 exposure could inhibit oxidative stress-related antioxidant enzymes (T-AOC, SOD, CAT and GPx) and increase the content of malondialdehyde (MDA) to cause oxidative stress. Secondly, BDE-47 enhanced mitochondrial division and inhibited fusion to induce mitochondrial membrane potential in CIK cells. BDE-47 enhanced the mRNA and protein levels of mitochondrial-pathway apoptosis related genes (Cas 3, Cyt-c, and BAX). Thirdly, BDE-47 treatment decreased the expression levels of mitochondrial-related regulatory factors AMPK-Sirt1-PGC-1α signal pathway. Intriguingly, BDE-47-induced oxidative stress, mitochondrial pathway apoptosis and mitochondrial dynamics disorder could be alleviated by MT treatment. Overall, we concluded that MT could relieve BDE-47-induced oxidative stress, mitochondrial dysfunction and apoptosis through the AMPK-Sirt1-PGC-1α axis. These results enrich the mechanisms of BDE-47 poisoning and reveal that MT treatment may be a potential strategy for solving BDE-47 poisoning.