title: Frataxin promotes antioxidant defense in a thiol-dependent manner resulting in diminished malignant transformation in vitro.
abstract: Friedreich ataxia is an inherited disorder caused by decreased expression of frataxin protein. Increasing evidence suggests that this protein might detoxify reactive oxygen species (ROS) by an unknown mechanism. Here we demonstrate that transgenic overexpression of human frataxin increases cellular antioxidant defense via activation of glutathione peroxidase and elevation of reduced thiols, thereby reducing the incidence of malignant transformation induced by ROS, as observed by soft agar assays and tumour formation in nude mice. These findings expand the understanding of antioxidant properties of frataxin, and tentatively suggest a role in the early induction of cancer.
authors.affiliation: Center for Molecular Medicine, Clinic III for Internal Medicine and Center for Physiology and Pathophysiology, University of Cologne, Germany.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Shoichet
authors.forename: Anselm T
authors.initials: AT
authors.lastname: Bäumer
authors.forename: Djordje
authors.initials: D
authors.lastname: Stamenkovic
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Dirk
authors.initials: D
authors.lastname: Müller-Wieland
authors.forename: Christoph
authors.initials: C
authors.lastname: Richter
authors.forename: Michael
authors.initials: M
authors.lastname: Ristow
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D005621:Friedreich Ataxia / Q000235:genetics*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism*; D066298:In Vitro Techniques; D033862:Iron-Binding Proteins; D051379:Mice; D018613:Microscopy, Confocal; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D019076:Transgenes; D000096923:Frataxin
chemical_list: D005979:Glutathione Peroxidase; D033862:Iron-Binding Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D000096923:Frataxin