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:
Aging
影响因子:
--
通讯作者:
Boriek AM
Boriek AM
中科院分区:
其他
文献类型:
--
作者:
Pardo PS;Boriek AM

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肌肉收缩与活性氧(ROS)的产生有关。清除ROS的机制是避免肌肉损伤的基础。我们之前在肌管中发现了一种拉伸诱导的遗传程序,它触发了一种抗氧化防御。在该机制的核心,早期生长反应蛋白Egr1转录激活SIRT1,通过SIRT1/FOXO途径激活Sod2,从而导致MnSOD活性增加。在这份报告中,我们展示了实验证据:a)Egr1和SIRT1蛋白在最大Sirt1诱导时间物理上相互作用,b)SIRT1对Egr1激活Sirt1启动子有负面影响。因此,Egr1和SIRT1之间的相互作用描述了一个自动调节环,该环关闭了拉伸诱导的Sirt1表达。
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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发表时间: 2002-01-01
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