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Updated: Jun 4, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Analysis of proteome changes in doxorubicin-treated adult rat cardiomyocyte
Suresh N Kumar1, Eugene A Konorev, Deepika Aggarwal
1Department of Pathology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Abstract:
Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity.
Insights
Doxorubicin (DOX) can cause heart damage in cancer patients by inducing apoptosis in cardiomyocytes. Protein changes related to oxidative stress may be key to this DOX cardiotoxicity.
Area of Science:
- Biochemistry
- Cardiology
- Oncology
Background:
- Doxorubicin (DOX) is a widely used chemotherapy agent with known cardiotoxicity.
- The mechanisms underlying DOX-induced cardiomyopathy involve reactive oxygen species, mitochondrial dysfunction, and cardiomyocyte apoptosis.
Purpose of the Study:
- To investigate the molecular mechanisms of Doxorubicin-induced cardiotoxicity at the protein level.
- To identify specific proteins and pathways affected by DOX exposure in cardiomyocytes and cardiac tissue.
Main Methods:
- Exposure of adult rat cardiomyocytes to low levels of DOX for 48 hours.
- Analysis of protein expression in DOX-treated cardiomyocytes and rat hearts using proteomic techniques.
- Application of a novel solubilization technique to monitor changes in low-abundance proteins.
Main Results:
- DOX exposure induced apoptosis in adult rat cardiomyocytes.
- Differential regulation of key proteins, including voltage-dependent anion-selective channel protein 2 and methylmalonate semialdehyde dehydrogenase, was observed.
- Proteomic analysis of DOX-treated rat hearts suggested nuclear accumulation of DOX.
- Altered protein expression, modification, and function related to oxidative stress response were identified.
Conclusions:
- Doxorubicin exposure leads to cardiomyocyte apoptosis and significant protein expression changes.
- Oxidative stress response pathways are critically involved in Doxorubicin cardiotoxicity.
- Further research into these protein alterations may reveal new therapeutic targets for mitigating DOX-induced heart damage.
