Apoptosis

, 13:1031

Involvement of JNK regulation in oxidative stress-mediated murine liver injury by microcystin-LR

  • Yinna Wei
  • Dan Weng
  • Feng Li
  • Xiao Zou
  • D. Owen Young
  • Jianguo Ji
  • Pingping Shen
Original Paper

DOI: 10.1007/s10495-008-0237-2

Cite this article as:
Wei, Y., Weng, D., Li, F. et al. Apoptosis (2008) 13: 1031. doi:10.1007/s10495-008-0237-2

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.

Keywords

ROSJNKProteomeMitochondriaApoptosisLiver injury

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Yinna Wei
    • 1
  • Dan Weng
    • 1
  • Feng Li
    • 1
  • Xiao Zou
    • 2
  • D. Owen Young
    • 1
    • 3
  • Jianguo Ji
    • 2
  • Pingping Shen
    • 1
  1. 1.State Key Laboratory of Pharmaceutical Biotechnology, School of Life ScienceNanjing UniversityNanjingPeople’s Republic of China
  2. 2.Proteome Group, National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life SciencesPeking UniversityBeijingPeople’s Republic of China
  3. 3.University of Rochester School of Medicine and DentistryRochesterUSA