Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy.
Loop diuretics affect skeletal myoblast differentiation and exercise-induced muscle hypertrophy.
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DOI：
10.1038/srep46369
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发表时间：
2017-04-18
影响因子：
4.6
通讯作者：
Uchida S
中科院分区：
文献类型：
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作者：
Mandai S;Furukawa S;Kodaka M;Hata Y;Mori T;Nomura N;Ando F;Mori Y;Takahashi D;Yoshizaki Y;Kasagi Y;Arai Y;Sasaki E;Yoshida S;Furuichi Y;Fujii NL;Sohara E;Rai T;Uchida S
肌肉萎缩或肌肉减少症导致癌症、肾衰竭或心力衰竭患者和老年人的发病率和死亡率。Na+-K+-2Cl−协同转运蛋白1（NKCC 1）在哺乳动物骨骼肌中高度表达，在那里它有助于产生膜离子电流和电位。然而，NKCC 1在肌发生中的生理功能尚不清楚。我们使用NKCC 1抑制剂布美他尼和呋塞米（它们是常用的髓袢利尿剂）研究了这个问题。在C2 C12小鼠骨骼肌成肌细胞分化过程中，NKCC 1蛋白水平增加，类似于肌生成标记物肌生成素和肌球蛋白重链（MHC）。NKCC 1抑制剂显著抑制成肌细胞融合成肌管和肌细胞生成素和MHC的表达。此外，磷酸化和总NKCC 1水平升高，在小鼠骨骼肌后6周的自愿轮运行。肌纤维横截面的免疫荧光分析显示，运动后更多的大肌纤维，但这是每天腹腔注射布美他尼（0.2或10毫克/公斤/天）受损。NKCC 1在肌生成和运动诱导的骨骼肌肥大中起重要作用，肾衰竭或心力衰竭患者的肌肉减少症可能归因于袢利尿剂治疗。
Muscle wasting or sarcopenia contributes to morbidity and mortality in patients with cancer, renal failure, or heart failure, and in elderly individuals. Na+-K+-2Cl− cotransporter 1 (NKCC1) is highly expressed in mammalian skeletal muscle, where it contributes to the generation of membrane ion currents and potential. However, the physiologic function of NKCC1 in myogenesis is unclear. We investigated this issue using the NKCC1 inhibitors bumetanide and furosemide, which are commonly used loop diuretics. NKCC1 protein levels increased during C2C12 murine skeletal myoblast differentiation, similarly to those of the myogenic markers myogenin and myosin heavy chain (MHC). NKCC1 inhibitors markedly suppressed myoblast fusion into myotubes and the expression of myogenin and MHC. Furthermore, phosphorylated and total NKCC1 levels were elevated in mouse skeletal muscles after 6 weeks’ voluntary wheel running. Immunofluorescence analyses of myofiber cross-sections revealed more large myofibers after exercise, but this was impaired by daily intraperitoneal bumetanide injections (0.2 or 10 mg/kg/day). NKCC1 plays an essential role in myogenesis and exercise-induced skeletal muscle hypertrophy, and sarcopenia in patients with renal or heart failure may be attributable to treatment with loop diuretics.