Doxorubicin treatment increased p53 protein levels in cardiomyocyte mitochondria and nuclei, a process regulated by redox state modulation via MnSOD and iNOS in genetically engineered mice.
Doxorubicin-induced cardiotoxicity may involve redox-dependent regulation of mitochondrial and nuclear p53 localization in cardiomyocytes.
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).
Nithipongvanitch et al. (Fri,) conducted a other in Doxorubicin-induced cardiotoxicity. Doxorubicin (Adriamycin) was evaluated on Mitochondrial and nuclear p53 localization in cardiomyocytes. Doxorubicin treatment increased p53 protein levels in cardiomyocyte mitochondria and nuclei, a process regulated by redox state modulation via MnSOD and iNOS in genetically engineered mice.