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Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction

Author

Listed:
  • Benjamin Steinhorn

    (Harvard Medical School)

  • Andrea Sorrentino

    (Harvard Medical School)

  • Sachin Badole

    (Harvard Medical School)

  • Yulia Bogdanova

    (Russian Academy of Sciences)

  • Vsevolod Belousov

    (Russian Academy of Sciences
    Pirogov Russian National Research Medical University
    Georg August University Göttingen)

  • Thomas Michel

    (Harvard Medical School)

Abstract

Oxidative stress plays an important role in the pathogenesis of many disease states. In the heart, reactive oxygen species are linked with cardiac ischemia/reperfusion injury, hypertrophy, and heart failure. While this correlation between ROS and cardiac pathology has been observed in multiple models of heart failure, the independent role of hydrogen peroxide (H2O2) in vitro and in vivo is unclear, owing to a lack of tools for precise manipulation of intracellular redox state. Here we apply a chemogenetic system based on a yeast D-amino acid oxidase to show that chronic generation of H2O2 in the heart induces a dilated cardiomyopathy with significant systolic dysfunction. We anticipate that chemogenetic approaches will enable future studies of in vivo H2O2 signaling not only in the heart, but also in the many other organ systems where the relationship between redox events and physiology remains unclear.

Suggested Citation

  • Benjamin Steinhorn & Andrea Sorrentino & Sachin Badole & Yulia Bogdanova & Vsevolod Belousov & Thomas Michel, 2018. "Chemogenetic generation of hydrogen peroxide in the heart induces severe cardiac dysfunction," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06533-2
    DOI: 10.1038/s41467-018-06533-2
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    Cited by:

    1. Maithily S. Nanadikar & Ana M. Vergel Leon & Jia Guo & Gijsbert J. Belle & Aline Jatho & Elvina S. Philip & Astrid F. Brandner & Rainer A. Böckmann & Runzhu Shi & Anke Zieseniss & Carla M. Siemssen & , 2023. "IDH3γ functions as a redox switch regulating mitochondrial energy metabolism and contractility in the heart," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Daan M. K. Soest & Paulien E. Polderman & Wytze T. F. Toom & Janneke P. Keijer & Markus J. Roosmalen & Tim M. F. Leyten & Johannes Lehmann & Susan Zwakenberg & Sasha Henau & Ruben Boxtel & Boudewijn M, 2024. "Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Shambhu Yadav & Markus Waldeck-Weiermair & Fotios Spyropoulos & Roderick Bronson & Arvind K. Pandey & Apabrita Ayan Das & Alexander C. Sisti & Taylor A. Covington & Venkata Thulabandu & Shari Caplan &, 2023. "Sensory ataxia and cardiac hypertrophy caused by neurovascular oxidative stress in chemogenetic transgenic mouse lines," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Gen Chen & Ning An & Jingling Shen & Huinan Chen & Yunjie Chen & Jia Sun & Zhicheng Hu & Junhui Qiu & Cheng Jin & Shengqu He & Lin Mei & Yanru Sui & Wanqian Li & Peng Chen & Xueqiang Guan & Maoping Ch, 2023. "Fibroblast growth factor 18 alleviates stress-induced pathological cardiac hypertrophy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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