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Citations to this article

The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy
Hagir B. Suliman, … , Karen E. Welty-Wolf, Claude A. Piantadosi
Hagir B. Suliman, … , Karen E. Welty-Wolf, Claude A. Piantadosi
Published November 21, 2007
Citation Information: J Clin Invest. 2007;117(12):3730-3741. https://doi.org/10.1172/JCI32967.
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Research Article Cardiology Article has an altmetric score of 7

The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy

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Abstract

The clinical utility of anthracycline anticancer agents, especially doxorubicin, is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse heart fails to upregulate the nuclear program for mitochondrial biogenesis and its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive wall stress and fibrosis. Furthermore, we exploited recent evidence that mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial pathology was averted by periodic CO inhalation, which restored mitochondrial biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis-inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis.

Authors

Hagir B. Suliman, Martha Sue Carraway, Abdelwahid S. Ali, Chrystal M. Reynolds, Karen E. Welty-Wolf, Claude A. Piantadosi

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 2 5 8 9 7 4 3 9 5 12 12 10 7 14 7 8 8 6 136
Citation information
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Citations to this article in year 2018 (9)

Title and authors Publication Year
Highly Potent Visnagin Derivatives Inhibit Cyp1 and Prevent Doxorubicin Cardiotoxicity
Aarti Asnani, Baohui Zheng, Yan Liu, You Wang, Howard Chen, Anita Vohra, An Chi, Ivan Cornella-Taracido, Huijun Wang, Douglas G. Johns, David Sosnovik, Randall Peterson
JCI Insight 2018
Carbon monoxide in lung cell physiology and disease
SW Ryter, KC Ma, AM Choi
American journal of physiology. Cell physiology 2018
Carbon Monoxide Ameliorates 6-Hydroxydopamine-Induced Cell Death in C6 Glioma Cells
H Moon, JH Jang, TC Jang, GH Park
Biomolecules & therapeutics 2018
Cardiovascular Disease in Survivors of Childhood Cancer: Insights Into Epidemiology, Pathophysiology, and Prevention
SH Armenian, GT Armstrong, G Aune, EJ Chow, MJ Ehrhardt, B Ky, J Moslehi, DA Mulrooney, PC Nathan, TD Ryan, HJ van der Pal, EC van Dalen, LC Kremer
Journal of Clinical Oncology 2018
Improvement of neuronal differentiation by carbon monoxide: Role of pentose phosphate pathway
AS Almeida, NL Soares, CO Sequeira, SA Pereira, U Sonnewald, HL Vieira
Redox Biology 2018
Protective effect of paracetamol in doxorubicin-induced cardiotoxicity in ischemia/reperfused isolated rat heart
M Hesari
Anatolian Journal of Cardiology 2018
Anthracycline Cardiotoxicity: Worrisome Enough to Have You Quaking?
D Bernstein
Circulation research 2018
Carbon monoxide-induced TFEB nuclear translocation enhances mitophagy/mitochondrial biogenesis in hepatocytes and ameliorates inflammatory liver injury
HJ Kim, Y Joe, SY Rah, SK Kim, SU Park, J Park, J Kim, J Ryu, GJ Cho, YJ Surh, SW Ryter, UH Kim, HT Chung
Cell Death and Disease 2018
Updates in Anthracycline-Mediated Cardiotoxicity
CG Nebigil, L Désaubry
Frontiers in pharmacology 2018

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