Mitochondrial and nuclear p53 localization in cardiomyocytes: Redox modulation by doxorubicin (adriamycin)?

被引：75

作者：

Nithipongvanitch, Ramaneeya

Ittarat, Wanida

Cole, Marsha P.

Tangpong, Jitbanjong

St. Clair, Daret K.

Oberley, Terry D. ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA

[2] Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand

[3] Univ Kentucky, Dept Toxicol, Lexington, KY 40506 USA

[4] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA

来源：

ANTIOXIDANTS & REDOX SIGNALING | 2007年 / 9卷 / 07期

关键词：

D O I：

10.1089/ars.2007.1632

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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).

引用

页码：1001 / 1008

页数：8

共 38 条

[1]

Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol γ [J].