RRC ID 65622
Author Alves de Souza RW, Gallo D, Lee GR, Katsuyama E, Schaufler A, Weber J, Csizmadia E, Tsokos GC, Koch LG, Britton SL, Wisløff U, Brum PC, Otterbein LE.
Title Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity.
Journal Cell Rep
Abstract 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.
Volume 35(3)
Pages 109018
Published 2021-4-20
DOI 10.1016/j.celrep.2021.109018
PII S2211-1247(21)00332-6
PMID 33882313
PMC PMC8196422
MeSH 5-Aminolevulinate Synthetase / genetics 5-Aminolevulinate Synthetase / metabolism Animals Ferrochelatase / genetics Ferrochelatase / metabolism Gene Expression Regulation Heme / metabolism* Heme Oxygenase-1 / deficiency Heme Oxygenase-1 / genetics* Isoenzymes / genetics Isoenzymes / metabolism Low Density Lipoprotein Receptor-Related Protein-1 / genetics Low Density Lipoprotein Receptor-Related Protein-1 / metabolism Male Membrane Proteins / deficiency Membrane Proteins / genetics* Membrane Proteins / metabolism Mice Mice, Inbred C57BL Mice, Knockout Mitochondria / genetics Mitochondria / metabolism Muscle Fibers, Skeletal / metabolism* Muscle Proteins / genetics Muscle Proteins / metabolism Muscular Atrophy / genetics* Muscular Atrophy / metabolism Muscular Atrophy / physiopathology MyoD Protein / genetics MyoD Protein / metabolism PAX7 Transcription Factor / genetics PAX7 Transcription Factor / metabolism Physical Conditioning, Animal / physiology* Signal Transduction Tripartite Motif Proteins / genetics Tripartite Motif Proteins / metabolism Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism
IF 8.109
Mice RBRC03163