title: Activation of autophagy protects against ROS-mediated mitochondria-dependent apoptosis in L-02 hepatocytes induced by Cr(VI).
abstract: BACKGROUND
  Hexavalent chromium (Cr(VI)) overdose causes hepatocellular injuries by inducing mitochondrial damage and subsequent apoptosis in animals and humans. Autophagy can selectively remove damaged organelles, especially impaired mitochondria, and in turn, protects against mitochondria-dependent cell death. The present study was designed to explore the effects of autophagy on the Cr(VI)-induced hepatotoxicity.
  
  
  METHODS
  L-02 hepatocytes were incubated with different concentrations of Cr(VI) for 24h and several indicators for evaluating mitochondrial damage and hepatocellular apoptosis were measured. Then effects of ROS scavenger NAC on ROS production and calcium overload during Cr(VI)-induced hepatotoxicity were examined. Finally, the study further investigated the role of autophagy played in repairing mitochondrial damage and subsequent hepatocyte injuries.
  
  
  RESULTS
  After exposed to different concentrations of Cr(VI) for 24h, cell viability, mitochondria membrane potential, ATP content were significantly decreased and caspase-3 activities and apoptosis rates increased in L-02 hepatocytes. The treatment of NAC reduced ROS formation and Ca(2+) content, restored CRAC channel activities and further diminished mitochondrial injuries. Furthermore, autophagy inducer, rapamycin is beneficial for repairing mitochondrial function and limiting hepatocytes damage, and pharmacological inhibition of autophagy by 3-methyladenine further exacerbated Cr(VI)-induced hepatotoxicity.
  
  
  CONCLUSIONS
  ROS production is a critical reason for Cr(VI)-induced mitochondria-dependent apoptosis. And activation of autophagy could repair mitochondria function to protect hepatocytes potentially by removing damaged mitochondria.
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Caigao
authors.initials: C
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D002857:Chromium / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008930:Mitochondria, Liver / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion