title: Iron chelation study in a normal human hepatocyte cell line suggests that tumor necrosis factor receptor-associated protein 1 (TRAP1) regulates production of reactive oxygen species.
abstract: Iron is an essential component of many proteins, and has crucial roles in the proper functioning of proteins involved in cellular respiration, proliferation, and differentiation. It has been recently reported that the deferoxamine (DFO), an iron chelator, induces mitochondrial dysfunction, characterized by an attenuation of oxidative phosphorylation, as well as senescence-like cellular morphology. However, the effects of DFO on mitochondrial heat shock proteins (HSPs) remain poorly understood. In this study, we examined the effect of DFO on tumor necrosis factor receptor-associated protein 1 (TRAP1), a representative mitochondrial HSP, in a normal human hepatocyte cell line, Chang cells. DFO specifically decreased TRAP1 levels, increasing reactive oxygen species (ROS) and caveolin-1 (Cav-1), a marker protein of senescence. To examine whether these effects of DFO are reversed, we established TRAP1-overexpressing Chang cells. DFO treatment to TRAP1-overexpressing cells resulted in decreases in levels of ROS, Cav-1, glutathione peroxidase (GPX), and manganese superoxide dismutase (MnSOD) levels as well as senescence-associated beta-galactosidase (SA beta-gal) activity. These results suggest that TRAP1 might play a role in protecting mitochondria against damaging stimuli via decrease of ROS generation.
authors.affiliation: Department of Biochemistry and Molecular Biology, ILCHUN Molecular Medicine Institute MRC, Seoul National University College of Medicine, Seoul 110-799, Seoul, Korea.
authors.forename: Chang-Nim
authors.initials: CN
authors.lastname: Im
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Seo
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D048430:Cell Shape; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018841:HSP90 Heat-Shock Proteins; D007502:Iron Chelating Agents; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C092306:TRAP1 protein, human; D003676:Deferoxamine