October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
Carbonylated cardiac myosin binding protein as a potential biomarker of doxorubicin-induced cardiotoxicity
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
FDA/CBER |
MOLBIO-2 |
Authors
- B. P. Aryal
- J. Jeong
- V. A. Rao
Abstract
Doxorubicin (Dox) is an anthracycline drug that is effectively used as a chemotherapeutic agent for various malignancies. Its dose-dependent oxidative stress and irreversible cardiac damage, however, has limited its chemoprotective properties in clinical practice. We hypothesized that the consequent protein oxidation under oxidative stress can be monitored and correlated with cellular outcome of survival or death. Based on our findings, we focused on protein carbonylation as an indicator of severe oxidative damage. First, to understand how Dox-induced oxidative stress is related to the cardiotoxicity, we detected a specific cardiac protein that was carbonylated under Dox-induced oxidative stress in a spontaneously hypertensive rat (SHR) model of acute toxicity. We identified this protein as a cardiac myosin binding protein C (MyBPC) using mass spectrometry. Consistent with the in vivo results, recombinant MyBPC also showed an increase in carbonylation under excessive oxidative conditions. We will present current evidence on the carbonylation of MyBPC in the context of its degradation under cardiotoxic conditions. Data from studies on the functional consequences of carbonylation in vitro will also be presented. Overall, our findings indicate the potential for a specific oxidative biomarker for monitoring the Dox-induced cardiotoxicity.
