Int J Biol Sci 2017; 13(7):888-900. doi:10.7150/ijbs.18468
Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells
1. Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China;
2. Wenzhou Municipal Key Laboratory of Emergency, Critical care, and Disaster Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China;
3. Department of Microbiology and immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325000, China;
4. Key Lab of Laboratory Medicine, Ministry of Education of China, Wenzhou 325000, China.
* The first two authors contributed equally to this study
Paraquat (PQ), as a highly effective and nonselective herbicide, induces cell apoptosis through generation of superoxide anions which forms reactive oxygen species (ROS). Mitochondria, as regulators for cellular redox signaling, have been proved to play an important role in PQ-induced cell apoptosis. This study aimed to evaluate whether and how mitochondrial fission interacts with oxidative stress in PQ-induced apoptosis in mouse alveolar type II (AT-II) cells. Firstly, we demonstrated that PQ promoted apoptosis and release of cytochrome-c (Cyt-c). Furthermore, we showed that PQ broke down mitochondrial network, enhanced the expression of fission-related proteins, increased Drp1 mitochondrial translocation while decreased the expression of fusion-related proteins in AT-II cells. Besides, inhibiting mitochondrial fission using mdivi-1, a selective inhibitor of Drp1, markedly attenuated PQ-induced apoptosis, release of Cyt-c and the generation of ROS. These results indicate that mitochondrial fission involves in PQ-induced apoptosis. Further study demonstrated that antioxidant ascorbic acid inhibited Drp1 mitochondrial translocation, mitochondrial fission and attenuated PQ-induced apoptosis. Overall, our findings suggest that mitochondrial fission interplays with ROS in PQ-induced apoptosis in mouse AT-II cells and mitochondrial fission could serve as a potential therapeutic target in PQ poisoning.
Keywords: paraquat, mitochondrial fission, apoptosis, oxidative stress, reactive oxygen species.
Zhao G, Cao K, Xu C, Sun A, Lu W, Zheng Y, Li H, Hong G, Wu B, Qiu Q, Lu Z. Crosstalk between Mitochondrial Fission and Oxidative Stress in Paraquat-Induced Apoptosis in Mouse Alveolar Type II Cells. Int J Biol Sci 2017; 13(7):888-900. doi:10.7150/ijbs.18468. Available from http://www.ijbs.com/v13p0888.htm