The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.

The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.
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DOI:
10.1002/mus.23924
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发表时间:
2014-03
期刊:
影响因子:
3.4
通讯作者:
Hannon, Kevin M.
Hannon, Kevin M.
中科院分区:
医学3区
文献类型:
--
作者:
Pond, Amber L.;Nedele, Carrie;Wang, Wen-Horng;Wang, Xun;Walther, Claire;Jaeger, Christine;Bradley, Kevin S.;Du, Huahua;Fujita, Naoya;Hockerman, Gregory H.;Hannon, Kevin M.

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研究了mERG 1a K+通道增加泛素蛋白酶体蛋白水解(UPP)的机制。后肢悬吊小鼠萎缩腓肠肌表达mERG 1a、MuRF 1和MAFbx基因。将mERG 1a电转移到非悬浮小鼠肌肉中显著降低了肌纤维大小(12.6%),并增加了UPP E3连接酶MuRF 1 mRNA(真实的时间PCR; 2.1倍)和蛋白质(免疫印迹; 23.7%),但不影响MAFbx E3连接酶表达。无活性HR-FOXO 3a(一种编码转录因子的基因,已知可通过直接结合其启动子诱导MAFbx表达)的共表达均未显著减少mERG 1a诱导的纤维大小减小或mERG 1a诱导的MuRF 1表达增加。mERG 1a K+通道显著增加MuRF 1的表达,但不增加MAFbx的表达。我们通过异位表达失活的FOXO 3a并显示其不参与mERG 1a介导的MuRF 1表达来探索这种表达模式。这些发现表明mERG 1a不通过AKT/FOXO通路调节MuRF 1表达。
The mechanism by which the mERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP) was investigated. Atrophic gastrocnemius muscles of hindlimb suspended mice express mERG1a, MuRF1 and MAFbx genes. Electro-transfer of mERG1a into non-suspended mouse muscle significantly decreases muscle fiber size (12.6%) and increases UPP E3ligase MuRF1 mRNA (real time PCR; 2.1 fold) and protein (immunoblot; 23.7%), but does not affect MAFbx E3ligase expression. Neither mERG1a-induced decreased fiber size nor mERG1a-induced increased MuRF1 expression is significantly curtailed by co-expression of inactive HR-FOXO3a, a gene encoding a transcription factor known to induce MAFbx expression by binding directly to its promoter. The mERG1a K+ channel significantly increases expression of MuRF1 but not MAFbx. We explored this expression pattern by ectopically expressing an inactive FOXO3a and showing that it is not involved in mERG1a-mediated expression of MuRF1. These findings suggest that mERG1a does not modulate MuRF1 expression through the AKT/FOXO pathway.
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