Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity

Rodrigo W. Alves de Souza; David Gallo; Ghee Rye Lee; Eri Katsuyama; Alexa Schaufler; Janick Weber; Eva Csizmadia; George C. Tsokos; Lauren G. Koch; Steven L. Britton; Ulrik Wisløff; Patricia C. Brum; Leo E. Otterbein

Cell Reports (Apr 2021)

Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity

Rodrigo W. Alves de Souza,
David Gallo,
Ghee Rye Lee,
Eri Katsuyama,
Alexa Schaufler,
Janick Weber,
Eva Csizmadia,
George C. Tsokos,
Lauren G. Koch,
Steven L. Britton,
Ulrik Wisløff,
Patricia C. Brum,
Leo E. Otterbein

Affiliations

Rodrigo W. Alves de Souza: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; School of Physical Education and Sport, University of São Paulo, São Paulo 05508030, Brazil
David Gallo: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Ghee Rye Lee: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Eri Katsuyama: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Alexa Schaufler: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Janick Weber: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Eva Csizmadia: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
George C. Tsokos: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Lauren G. Koch: Department of Physiology & Pharmacology, The University of Toledo, Toledo, OH 43606, USA
Steven L. Britton: Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
Ulrik Wisløff: K.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim 7491, Norway
Patricia C. Brum: School of Physical Education and Sport, University of São Paulo, São Paulo 05508030, Brazil
Leo E. Otterbein: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA; Corresponding author

Journal volume & issue: Vol. 35, no. 3
p. 109018

Abstract

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Summary: Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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