Research Paper Volume 4, Issue 7 pp 456—461
An autoregulatory loop reverts the mechanosensitive Sirt1 induction by EGR1 in skeletal muscle cells
- 1 Department of Medicine, Division of Pulmonary, Critical Care and Sleep, Baylor College of Medicine
- 2 Department of Cell and Molecular Biology, Baylor College of Medicine, Houston, TX 77030
Received: June 1, 2012 Accepted: July 17, 2012 Published: July 18, 2012
https://doi.org/10.18632/aging.100470How to Cite
Abstract
Muscle contraction is associated with the production of reactive oxygen species (ROS). Mechanisms of ROS scavenging are fundamental to avoid muscle damage. We had previously discovered a stretch-induced genetic program in myotubes that triggers an antioxidant defense. At the core of this mechanism, transcriptional activation of SIRT1 by the early growth response protein EGR1 results in increased MnSOD activity through the activation of Sod2 by SIRT1/FOXO pathway. In this report, we show experimental evidence that; a) EGR1 and SIRT1 proteins physically interact at the time of maximal Sirt1 induction, b) SIRT1 has a negative effect on the activation of the Sirt1 promoter by EGR1. Thus, the interaction between EGR1 and SIRT1 describes an autoregulatory loop that shuts down the stretch-induced Sirt1 expression.
Abbreviations
ROS: reactive oxygen species; SIRT1: sirtuin 1; EGR1: early growth response protein 1; FOXO: Forkhead box protein O; SOD2: Superoxide dismutase 2; MnSOD: manganese-dependent superoxide dismutase.