Daunorubicin therapy is associated with upregulation of E3 ubiquitin ligases in the heart

Experimental Biology and Medicine
Balindiwe J N SishiAnna-Mart Engelbrecht

Abstract

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 ...Continue Reading

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Citations

Sep 12, 2014·The Journal of Pharmacy and Pharmacology·Oktay TacarCrispin R Dass
May 4, 2013·Toxicology·Balindiwe J N SishiAnna-Mart Engelbrecht
Jun 8, 2014·Experimental Cell Research·Biljana RisticLjubica Harhaji-Trajkovic
Apr 27, 2017·Oncotarget·Navid Koleini, Elissavet Kardami
Nov 6, 2012·Current Opinion in Supportive and Palliative Care
Jul 18, 2021·Journal of Biochemical and Molecular Toxicology·Khalid AlhazzaniMohammed Alswayyed

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Methods Mentioned

BETA
ubiquitination
electrophoresis
lipidation

Software Mentioned

SCAN
IT

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