title: Role of mitochondrial electron transport chain dysfunction in Cr(VI)-induced cytotoxicity in L-02 hepatocytes.
abstract: BACKGROUND
  Hexavalent chromium [Cr(VI)] and its compounds (e.g. chromates), which are extensively used in numerous industrial processes including leather tanning and steel manufacturing, are considered as priority pollutants. There is growing evidence supporting that Cr(VI) could be a human carcinogen that induces primary liver cancer after oral exposure, and this sheds light on the importance of the investigation of Cr(VI)-induced hepatotoxicity. Although it is known that mitochondria are major targets for heavy metals, the mechanisms of electron transfer chain (ETC) dysfunction involved in Cr(VI)-induced cytotoxicity are unclear.
  
  
  METHODS
  In the present study, by using mitochondrial respiratory chain complex (MRCC) I inhibitor rotenone (ROT) and its substrates glutamate/malate (Glu/Mal), MRCC III inhibitor antimycin A (AA) and its substrate coenzyme Q (CoQ), and the antioxidant Vitamin C (Vit C), we aimed to elucidate the role of mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity.
  
  
  RESULTS
  We found that Cr(VI) targeted and inhibited MRCC I and III to induce ETC dysfunction, which played an important role in Cr(VI)-induced cytotoxicity.
  
  
  CONCLUSIONS
  Our current data provides novel important insight into the mechanisms of mitochondrial ETC dysfunction in Cr(VI)-induced cytotoxicity in the hepatocytes, and we will be poised to develop new methods in the prevention and treatment of liver diseases involving mitochondrial ETC dysfunction for the occupational exposure population.
authors.affiliation: Department of Biochemistry, School of Life Sciences, Central South University, Changsha, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: An
authors.initials: A
authors.lastname: Wang
authors.forename: Hanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Caigao
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000968:Antimycin A / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002857:Chromium / Q000633:toxicity*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity; D013379:Substrate Specificity
chemical_list: D012402:Rotenone; D002857:Chromium; C074702:chromium hexavalent ion; D000968:Antimycin A; D000255:Adenosine Triphosphate; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D001205:Ascorbic Acid; D010100:Oxygen