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- Title
Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts.
- Authors
Sardão, Vilma A.; Oliveira, Paulo J.; Holy, Jon; Oliveira, Catarina R.; Wallace, Kendall B.
- Abstract
Doxorubicin (DOX) is a widely prescribed chemotherapeutic. The hypothesis for the present study is that DOX-induced myocyte apoptosis involves mitochondrial dysfunction that is a consequence of nuclear DOX effects. H9c2 myoblasts were incubated with 0, 0.5 and 1 μM DOX and nuclear and mitochondrial alterations were determined. Doxorubicin accumulation in the nucleus was detected after 3 h treatment, followed by an increase in p53 and a decrease in mitochondrial membrane potential. Apoptotic markers, such as caspase activation and chromatin condensation were detected after 24 h of DOX treatment. Bax and p53 translocation to mitochondria as well as the formation of Bax clusters in the cytosol were observed. Importantly, pifithrin-alpha, a p53 inhibitor, protected against DOX-induced mitochondrial depolarization, caspase activation and cell death. Mitochondrial dysfunction in H9c2 myoblasts treated with DOX is a consequence of nuclear p53 activation rather than a direct effect of the drug on mitochondria.
- Subjects
RESEARCH; DOXORUBICIN; CARDIOMYOPATHIES; OXIDATIVE stress; MITOCHONDRIA; CELL death
- Publication
Cancer Chemotherapy & Pharmacology, 2009, Vol 64, Issue 4, p811
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-009-0932-x