title: H(2)O(2) induces translocation of APE/Ref-1 to mitochondria in the Raji B-cell line.
abstract: Reactive oxygen species (ROS) are generated as by-products of respiration and are used as signal transducing intermediates in out-in signaling pathways. ROS are also generated during inflammatory responses and it has been shown that hydrogen peroxide may trigger activation of B-lymphocytes, similar to cross-linking of surface immunoglobulins. On the other hand, both exogenous and endogenous generated ROS are a major source of nuclear and mitochondrial DNA (mtDNA) damage. The base excision repair (BER) enzyme APE/Ref-1 normally repairs small nuclear DNA lesion such as oxidized or alkylated bases. It is not clear though whether DNA repair mechanisms able to abolish oxidative damage from nuclear DNA are present into mitochondria too. Here we show by confocal microscopy and Western blot analysis that in the B-lymphocyte Raji cell line a fraction of APE/Ref-1 rapidly re-localizes into mitochondria following H(2)O(2) activation. Targeting of APE/Ref-1 to mitochondria is not associated with cytochrome-c loss or apoptosis induction. These findings indicate that the APE/Ref-1 translocates to mitochondria in response to oxidative stress and thereby it might exert a protective function.
authors.affiliation: Immunology Section, Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
authors.forename: Paola
authors.initials: P
authors.lastname: Spessotto
authors.forename: Alfonso
authors.initials: A
authors.lastname: Colombatti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Vitale
authors.forename: Carlo
authors.initials: C
authors.lastname: Pucillo
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D001693:Biological Transport, Active; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015534:Trans-Activators / Q000032:analysis; D015533:Transcriptional Activation / Q000187:drug effects; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D051176:beta Catenin; D006861:Hydrogen Peroxide; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase