title: TorsinA protects against oxidative stress in COS-1 and PC12 cells.
abstract: Dystonia is a highly frequent movement disorder, the pathogenesis of which remains unclear. The cloning of TorsinA, the gene responsible for early-onset dystonia, was a major breakthrough. However, the function of this protein remains unclear. By sequence homology, TorsinA belongs to the ATPases associated with diverse cellular activities-family, many of whose members are chaperones and/or proteases. We report here that in an in vitro model for oxidative stress, H2O2 treatment, overexpression of TorsinA was protective against cell death. COS-1 cells overexpressing TorsinA demonstrated drastically reduced terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling-staining following exposure to H2O2. Furthermore, transfection with TorsinA significantly increased survival of PC12 after H2O2 treatment. To our knowledge, this is the first demonstration that TorsinA protects against oxidative stress. We speculate that a loss of this cellular function in mutant TorsinA may be linked to the pathogenesis of early-onset dystonia.
authors.affiliation: Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Peter
authors.initials: P
authors.lastname: Teismann
authors.forename: Annette
authors.initials: A
authors.lastname: Trutzel
authors.forename: Jomana
authors.initials: J
authors.lastname: Naim
authors.forename: Angelika
authors.initials: A
authors.lastname: Richter
authors.forename: Nicole
authors.initials: N
authors.lastname: Schmidt
authors.forename: Oliver
authors.initials: O
authors.lastname: von Ahsen
authors.forename: Alfred
authors.initials: A
authors.lastname: Bach
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival; D004421:Dystonia / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D018832:Molecular Chaperones; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D051028:bcl-2-Associated X Protein
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C491549:Tor1a protein, rat; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide