An autoregulatory loop reverts the mechanosensitive Sirt1 induction by EGR1 in skeletal muscle cells.
An autoregulatory loop reverts the mechanosensitive Sirt1 induction by EGR1 in skeletal muscle cells.
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DOI:
10.18632/aging.100470
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发表时间:
2012-07
期刊:
影响因子:
--
通讯作者:
Boriek AM
中科院分区:
文献类型:
--
作者:
Pardo PS;Boriek AM
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.
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