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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Daunorubicin therapy is associated with upregulation of E3 ubiquitin ligases in the heart
Experimental Biology and Medicine, Volume 237, No. 2, Year 2012
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Description
Daunorubicin (DNR) and doxorubicin (DOX) are two of the most effective anthracycline drugs known for the treatment of systemic neoplasms and solid tumors. However, their clinical use is hampered due to profound cardiotoxicity. The mechanism by which DNR injures the heart remains to be fully elucidated. Recent reports have indicated that DOX activates ubiquitin proteasome-mediated degradation of specific transcription factors; however, no reports exist on the effect of DNR on the E3 ubiquitin ligases, MURF-1 (muscle ring finger 1) and MAFbx (muscle atrophy F-box). The aim of this study was to investigate the effect of DNR treatment on the protein and organelle degradation systems in the heart and to elucidate some of the signalling mechanisms involved. Adult rats were divided into two groups where one group received six intraperitoneal injections of 2 mg/kg DNR on alternate days and the other group received saline injections as control. Hearts were excised and perfused on a working heart system the day after the last injection and freeze-clamped for biochemical analysis. DNR treatment significantly attenuated cardiac function and increased apoptosis in the heart. DNR-induced cardiac cytotoxicity was associated with upregulation of the E3 ligases, MURF-1 and MAFbx and also caused significant increases in two markers of autophagy, beclin-1 and LC3. These changes observed in the heart were also associated with attenuation of the phosphoinositide 3-kinase/Akt signalling pathway. © 2012 by the Society for Experimental Biology and Medicine.
Authors & Co-Authors
Sishi, Balindiwe J.N.
South Africa, Stellenbosch
Stellenbosch University
Bester, Dirk J.
South Africa, Bellville
Cape Peninsula University of Technology
Wergeland, Anita
Norway, Bergen
Universitetet I Bergen
Loos, Ben
South Africa, Stellenbosch
Stellenbosch University
Jonassen, Anne Kristine
Norway, Bergen
Universitetet I Bergen
van Rooyen, Jacques
South Africa, Bellville
Cape Peninsula University of Technology
Engelbrecht, Anna Mart
South Africa, Stellenbosch
Stellenbosch University
Statistics
Citations: 19
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1258/ebm.2011.011106
ISSN:
15353702
e-ISSN:
15353699
Research Areas
Cancer
Health System And Policy
Noncommunicable Diseases