AMPK and glucose deprivation exert an isoform-specific effect on the expression of Na+,K+-ATPase subunits in cultured myotubes.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-09-01 Epub Date: 2024-05-06 DOI:10.1007/s10974-024-09673-9
Anja Vidović, Klemen Dolinar, Alexander V Chibalin, Sergej Pirkmajer
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引用次数: 0

Abstract

In skeletal muscle, Na+,K+-ATPase (NKA), a heterodimeric (α/β) P-type ATPase, has an essential role in maintenance of Na+ and K+ homeostasis, excitability, and contractility. AMP-activated protein kinase (AMPK), an energy sensor, increases the membrane abundance and activity of NKA in L6 myotubes, but its potential role in regulation of NKA content in skeletal muscle, which determines maximum capacity for Na+ and K+ transport, has not been clearly delineated. We examined whether energy stress and/or AMPK affect expression of NKA subunits in rat L6 and primary human myotubes. Energy stress, induced by glucose deprivation, increased protein content of NKAα1 and NKAα2 in L6 myotubes, while decreasing the content of NKAα1 in human myotubes. Pharmacological AMPK activators (AICAR, A-769662, and diflunisal) modulated expression of NKA subunits, but their effects only partially mimicked those that occurred in response to glucose deprivation, indicating that AMPK does not mediate all effects of energy stress on NKA expression. Gene silencing of AMPKα1/α2 increased protein levels of NKAα1 in L6 myotubes and NKAα1 mRNA levels in human myotubes, while decreasing NKAα2 protein levels in L6 myotubes. Collectively, our results suggest a role for energy stress and AMPK in modulation of NKA expression in skeletal muscle. However, their modulatory effects were not conserved between L6 myotubes and primary human myotubes, which suggests that coupling between energy stress, AMPK, and regulation of NKA expression in vitro depends on skeletal muscle cell model.

Abstract Image

AMPK和葡萄糖剥夺对培养肌管中Na+,K+-ATP酶亚基的表达具有同工酶特异性影响。
在骨骼肌中,Na+,K+-ATP 酶(NKA)是一种异源二聚体(α/β)P 型 ATP 酶,在维持 Na+ 和 K+ 平衡、兴奋性和收缩性方面发挥着重要作用。能量传感器 AMP 激活蛋白激酶(AMPK)能增加 L6 肌管中 NKA 的膜丰度和活性,但它在调节骨骼肌中 NKA 含量(它决定了 Na+ 和 K+ 转运的最大能力)方面的潜在作用尚未明确界定。我们研究了能量应激和/或 AMPK 是否会影响大鼠 L6 肌管和原代人类肌管中 NKA 亚基的表达。通过葡萄糖剥夺诱导的能量应激增加了 L6 肌管中 NKAα1 和 NKAα2 的蛋白含量,而降低了人肌管中 NKAα1 的含量。药理 AMPK 激活剂(AICAR、A-769662 和二氟尼沙)可调节 NKA 亚基的表达,但它们的效应仅部分模拟了葡萄糖剥夺时的效应,这表明 AMPK 并未介导能量应激对 NKA 表达的所有效应。AMPKα1/α2的基因沉默增加了L6肌管中NKAα1的蛋白水平和人肌管中NKAα1的mRNA水平,同时降低了L6肌管中NKAα2的蛋白水平。总之,我们的研究结果表明,能量应激和 AMPK 在调节骨骼肌中 NKA 的表达方面发挥作用。然而,它们的调节作用在 L6 肌管和原代人类肌管之间并不一致,这表明能量应激、AMPK 和体外 NKA 表达调节之间的耦合取决于骨骼肌细胞模型。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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