Document Detail

New insights into doxorubicin-induced cardiotoxicity: the critical role of cellular energetics.
MedLine Citation:
PMID:  16879835     Owner:  NLM     Status:  MEDLINE    
Cardiotoxic side-effects represent a serious complication of anticancer therapy with anthracyclines, in particular with doxorubicin (DXR) being the leading drug of the group. Different hypotheses, accentuating various mechanisms and/or targets, have been proposed to explain DXR-induced cardiotoxicity. This review focuses on the myocardial energetic network as a target of DXR toxic action in heart and highlights the recent advances in understanding its role in development of the DXR related cardiac dysfunction. We present a survey of DXR-induced defects in different steps of cardiac energy metabolism, including reduction of oxidative capacity of mitochondria, changes in the profile of energy substrate utilization, disturbance of energy transfer between sites of energy production and consumption, as well as defects in energy signaling. Considering the wide spectrum and diversity of the changes reported, we attempt to integrate these facts into a common framework and to discuss important functional and temporal relationships between DXR-induced events and the possible underlying molecular mechanisms.
Malgorzata Tokarska-Schlattner; Michael Zaugg; Christian Zuppinger; Theo Wallimann; Uwe Schlattner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2006-08-01
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  41     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-15     Completed Date:  2007-02-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  389-405     Citation Subset:  IM    
Institute of Cell Biology, ETH Zurich, Hönggerberg HPM D24, CH-8093 Zürich, Switzerland.
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MeSH Terms
AMP-Activated Protein Kinases
Anthracyclines / pharmacology
Antibiotics, Antineoplastic / pharmacology
Creatine Kinase / metabolism
Doxorubicin / adverse effects*
Heart / drug effects*
Heart Diseases / chemically induced,  pathology
Models, Biological
Multienzyme Complexes / metabolism
Myocardium / metabolism,  pathology*
Phosphates / metabolism
Protein-Serine-Threonine Kinases / metabolism
Reg. No./Substance:
0/Anthracyclines; 0/Antibiotics, Antineoplastic; 0/Multienzyme Complexes; 0/Phosphates; 23214-92-8/Doxorubicin; EC Protein Kinases; EC Kinases; EC Kinase

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