title: Mitochondrial and nuclear p53 localization in cardiomyocytes: redox modulation by doxorubicin (Adriamycin)?
abstract: Reactive oxygen (ROS) and nitrogen species (RNS) generation have been proposed to be an important mechanism of doxorubicin (Adriamycin; ADR)-induced cardiotoxicity and cardiomyocyte apoptosis, processes that may be mediated by p53 protein. We note that ADR treatment resulted in increased levels of p53 protein in cardiomyocyte mitochondria and nuclei. Modulation of the cardiomyocyte redox state in genetically engineered mice by modulation of enzymes involved in metabolism of ROS/RNS, manganese superoxide dismutase (MnSOD), or inducible nitric oxide synthase (iNOS), or a combination of these, regulated levels of mitochondrial/nuclear p53 in cardiomyocytes after ADR administration. These observations led to the hypothesis that mitochondrial/nuclear p53 localization and function in the cardiomyocyte response to ADR may be regulated through redox-dependent mechanism(s).
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.
authors.forename: Ramaneeya
authors.initials: R
authors.lastname: Nithipongvanitch
authors.forename: Wanida
authors.initials: W
authors.lastname: Ittarat
authors.forename: Marsha P
authors.initials: MP
authors.lastname: Cole
authors.forename: Jitbanjong
authors.initials: J
authors.lastname: Tangpong
authors.forename: Daret K St
authors.initials: DK
authors.lastname: Clair
authors.forename: Terry D
authors.initials: TD
authors.lastname: Oberley
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin