Oxidative stress activates the Nrf2-mediated antioxidant response and P38 MAPK pathway: A possible apoptotic mechanism induced by BDE-47 in rainbow trout (Oncorhynchus mykiss) gonadal RTG-2 cells
2021
Zhou, Zhongyuan | Zhou, Bin | Chen, Hongmei | Lu, Keyu | Wang, You
Our previous study showed that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), the most biotoxic polybrominated diphenyl ether (PBDE) in the marine environment, induced apoptosis in rainbow trout gonadal RTG-2 cells. This effect occurred via ROS- and Ca²⁺-mediated apoptotic pathways, but the exact mechanism remains unknown. Therefore, in the present study, the possible mechanism was examined from the perspective of ROS-induced oxidative stress. The results showed that BDE-47 exposure significantly elevated the malondialdehyde (MDA) contents and the intracellular GSH/GSSG ratio, and the GSH-related enzymes were greatly altered, indicating alteration of the redox status and occurrence of oxidative stress. The mRNA levels of nuclear factor E2-related factor 2 (Nrf2) and its downstream genes were simultaneously greatly elevated. The p38 mitogen-activated protein kinase (MAPK) signaling pathway was also found to be induced by BDE-47 exposure. The addition of SB203580, a p38 MAPK inhibitor resulted in decreased apoptosis. In addition, supplementation with Ca²⁺ inhibitors BAPTA-AM positively affected p38 MAPK activation. Taken together, BDE-47 exposure resulted in the occurrence of oxidative stress and initiated the Nrf2-mediated antioxidant response. Subsequently, the altered redox status induced p38 MAPK activation, which played a pivotal role in the cellular apoptosis of RTG-2 cells.
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