The aim of the study was to verify the thesis that the cardiotoxic effects of doxorubicin are connected with activation of the ubiquitin - proteasome pathway followed by protein degradation. The expression of myocardial damage markers - fatty acid binding protein (H-FABP) and brain natriuretic peptide (BNP) was evaluated in rat fetal cardiomyocytes simultaneously treated with doxorubicin and the proteasome inhibitor - bortezomib. The level of H-FABP and BNP protein under the influence of doxorubicin was decreased below the detection threshold with unchanged (H-FABP) or elevated (BNP) mRNA expression level. Against the expectations, the inhibitor of proteasome did not abolish this effect. The observed abnormal expression of BNP and H-FABP protein after doxorubicin treatment makes their diagnostic significance in anthracycline cardiotoxicity questionable.
1. Adams J.: Development of the Proteasome Inhibitor PS-341. The Oncologist, 7, 9, 2002.
2. Aihara Y. et al.: Doxorubicin Represses CARP Gene Transcription Through the Generation of Oxidative Stress in Neonatal Rat Cardiac Myocytes: Possible Role of Serine/Threonine Kinase - dependent Pathways. J. Mol. Cell Cardiol., 32, 1401, 2000.
3. Batheja R. et al.: Paradoxical decrease in plasma N-terminal-proBNP (NTproBNP) levels in patients receiving doxorubicin chemotherapy and declining left ventricular ejection fraction. J. Am. Coll. Cardiol., 47, 66A, 2006.
Financed by the National Centre for Research and Development under grant No. SP/I/1/77065/10 by the strategic scientific research and experimental development program:
SYNAT - “Interdisciplinary System for Interactive Scientific and Scientific-Technical Information”.