Induction of Sirt1 by mechanical stretch of skeletal muscle through the early response factor EGR1 triggers an antioxidative response.
Mechanical loading of muscles by intrinsic muscle activity or passive stretch leads to an increase in the production of reactive oxygen species. The NAD-dependent protein deacetylase SIRT1 is involved in the protection against oxidative stress by enhancing FOXO-driven Sod2 transcription. In this report, we unravel a mechanism triggered by mechanical stretch of skeletal muscle cells that leads to an EGR1-dependent transcriptional activation of the Sirt1 gene. The resulting transient increase in SIRT1 expression generates an antioxidative response that contributes to reactive oxygen species scavenging.
Division of Pulmonary, Critical Care Medicine, and Sleep, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Patricia S
PS
Pardo
Junaith S
JS
Mohamed
Michael A
MA
Lopez
Aladin M
AM
Boriek
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D032342:Muscle Cells / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D052580:Muscle Stretching Exercises; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology; D000099156:Superoxide Dismutase 2
D000975:Antioxidants; D051766:Early Growth Response Protein 1; D009124:Muscle Proteins; D017382:Reactive Oxygen Species; D056564:Sirtuin 1; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C486109:Egr1 protein, mouse; C470545:Sirt1 protein, mouse