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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 2015 (12)

Title and authors Publication Year
Krüppel-like factor 6 regulates mitochondrial function in the kidney
Sandeep Mallipattu, Sylvia Horne, Vivette D'Agati, Goutham Narla, Ruijie Liu, Michael A. Frohman, Kathleen Dickman, Edward Chen, Avi Ma'ayan, Agnieszka Bialkowska, Amr M. Ghaleb, Mandayam Nandan, Mukesh Jain, Ilse Daehn, Peter Chuang, Vincent Yang, John He
Journal of Clinical Investigation 2015
Therapeutic targeting of autophagy in cardiovascular disease
GG Schiattarella, JA Hill
Journal of Molecular and Cellular Cardiology 2015
Mitochondrial Quality Control as a Therapeutic Target
HB Suliman, CA Piantadosi, MP Mattson
Pharmacological reviews 2015
Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1
CS Kim, Y Kwon, SY Choe, SM Hong, H Yoo, T Goto, T Kawada, HS Choi, Y Joe, HT Chung, R Yu
Nutrition & Metabolism 2015
HO-1/CO regulation of mitochondrial-capillary density relationships in human skeletal muscle
SR Pecorella, JV Potter, AD Cherry, DF Peacher, KE Welty-Wolf, RE Moon, CA Piantadosi, HB Suliman
American journal of physiology. Lung cellular and molecular physiology 2015
Friend or foe? Carbon monoxide and the mitochondria
N Schallner, LE Otterbein
Frontiers in physiology 2015
Carbon monoxide and mitochondria—modulation of cell metabolism, redox response and cell death
AS Almeida, CÃ Figueiredo-Pereira, HL Vieira
Frontiers in physiology 2015
MicroRNA-532-3p regulates mitochondrial fission through targeting apoptosis repressor with caspase recruitment domain in doxorubicin cardiotoxicity
JX Wang, XJ Zhang, C Feng, T Sun, K Wang, Y Wang, LY Zhou, PF Li
Cell Death and Disease 2015
Cyclovirobuxine D Attenuates Doxorubicin-Induced Cardiomyopathy by Suppression of Oxidative Damage and Mitochondrial Biogenesis Impairment
Q Guo, J Guo, R Yang, H Peng, J Zhao, L Li, S Peng
Oxidative medicine and cellular longevity 2015
Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation
H Gomez, B Kautza, D Escobar, I Nassour, J Luciano, AM Botero, L Gordon, S Martinez, A Holder, O Ogundele, P Loughran, MR Rosengart, M Pinsky, S Shiva, BS Zuckerbraun, R Raju
PloS one 2015
Redox mechanisms of cardiomyocyte mitochondrial protection
RR Bartz, HB Suliman, CA Piantadosi
Frontiers in physiology 2015
Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism - a role for Ca 2+ ?: Mitochondria and carbon monoxide
SR Oliveira, CS Queiroga, HL Vieira
The Journal of Physiology 2015

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