Abstract | PURPOSE: METHODS: RESULTS:
Doxorubicin-induced heart failure was associated with significant decreases in UCP2 and UCP3 protein expression compared with nonfailing hearts (P < 0.05). While the rates of state 3 and state 4 respiration and ATP synthesis were lower in mitochondria isolated from failing hearts, the respiratory control ratio was 15% higher (P < 0.05), and the ratio of ATP production to oxygen consumption was 25% higher (P < 0.05) in mitochondria from failing hearts, indicating greater coupling between citric acid cycle flux and mitochondrial ATP synthesis. However, the decrease in UCP expression was associated with 50% greater mitochondrial ROS generation (P < 0.05). CONCLUSIONS: Downregulation of myocardial UCP2 and UCP3 in the setting of doxorubicin-induced heart failure is associated with improved efficiency of ATP synthesis, which might compensate for abnormal energy metabolism. However, this beneficial effect is counterbalanced by greater oxidant stress.
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Authors | Heiko Bugger, Cinthia Guzman, Christoph Zechner, Monica Palmeri, Kerry S Russell, Raymond R Russell 3rd |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 67
Issue 6
Pg. 1381-8
(Jun 2011)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 20809120
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibiotics, Antineoplastic
- Ion Channels
- Mitochondrial Proteins
- Reactive Oxygen Species
- Ucp2 protein, mouse
- Ucp2 protein, rat
- Ucp3 protein, mouse
- Ucp3 protein, rat
- Uncoupling Protein 2
- Uncoupling Protein 3
- Doxorubicin
- Adenosine Triphosphate
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Topics |
- Adenosine Triphosphate
(biosynthesis)
- Animals
- Antibiotics, Antineoplastic
(toxicity)
- Down-Regulation
- Doxorubicin
(toxicity)
- Heart Failure
(chemically induced, metabolism, physiopathology)
- In Vitro Techniques
- Ion Channels
(biosynthesis)
- Male
- Mice
- Mitochondria, Heart
(drug effects, metabolism)
- Mitochondrial Proteins
(biosynthesis)
- Myocardium
(metabolism, pathology)
- Rats
- Rats, Sprague-Dawley
- Reactive Oxygen Species
(metabolism)
- Uncoupling Protein 2
- Uncoupling Protein 3
- Ventricular Function, Left
(drug effects)
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