Abstract
Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce various liver diseases via oxidative stress. However, the underlying mechanisms are largely unknown. In the current study, we investigated the molecular events involved in the oxidative liver injury by MC-LR. Our results demonstrated that MC-LR induced liver injury in mice through a series of steps that began with the production of reactive oxygen species (ROS), which stimulated the sustained activation of JNK and its downstream targets, AP-1 and Bid. Furthermore, the mitochondrial proteomic analysis indicated that JNK activation affected some crucial enzymes of energy metabolism, led to mitochondria dysfunction, which contributed to hepatocyte apoptosis and oxidative liver injury by MC-LR. Our results reveal significant insights into the mechanisms of liver injury induced by microcystins, and serve as a framework for deciphering the role of JNK in oxidative stress-associated liver diseases.
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Acknowledgements
We thank Prof. Ning Su from the School of Basic Medical Sciences, Southeast University, for excellent technical assistance. This work was supported by the National Natural Science Foundation of China (Project No. 30571538), the Key Project of Chinese Ministry of Education (No. 107049), the Natural Science Foundation of Jiangsu Province (No. BK2006120), and the National Basic Research Program of China (No.2006CB910103). The authors declare that they have no conflict of interest.
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Yinna Wei and Dan Weng equally contributed to this work.
D. Owen Young—An international exchange student from USA.
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Wei, Y., Weng, D., Li, F. et al. Involvement of JNK regulation in oxidative stress-mediated murine liver injury by microcystin-LR. Apoptosis 13, 1031–1042 (2008). https://doi.org/10.1007/s10495-008-0237-2
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DOI: https://doi.org/10.1007/s10495-008-0237-2