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Analysis of molecular mechanism on the training effects using prohibited doping drugs

禁用兴奋剂药物对训练效果影响的分子机制分析

基本信息

批准号：
17500421
负责人：
KITAURA Takashi
金额：
$ 2.37万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17500421/
关键词：
doping differentiation Notch Signaling Delta-like1 Jagged1 Satellite cells clenbuterol Numb 薬理学生理学筋芽細胞 MyoDファミリー Notchシグナル Delta-like1 Myostatin Numb IGF-1

项目摘要

Clenbuterol is one of the beta-2 adrenergic receptor agonists with powerful muscle anabolic effects and is prohibited to use as doping drug for athletes. Recently it is well documented that the muscle hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number. And it is established that Notch1 becomes activated in satellite cells as they progress from a state of quiescence to one of active proliferation as myogenic precursor cells. However, we already reported that the Notch 1 mRNA showed no changes in both SOL and EDL. Furthermore, the effect of clenbuterol on the Numb, a plasma membrane-associated cytoplasmic protein, regulating differentiation of satellite cells is still not clear. In this study, we tried to examine the hypertrophic effects of clenbuterol on the Numb regulating system of both fast-and slow-twitch muscles. It is said that clenbuterol increased the MyoD as the myogenic master regulator and might induce the muscle … More hypertrophy and the transformation from slow-to fast-twitch muscle.The muscle wet weights increased in both SOL and EDL muscles with clenbuterol. The myogenin mRNA showed the increase in both muscles. The MyoD mRNA increased drastically in SOL. They may explained the accumulated fast-twitch fibers with fiber type transition from slow-to-fast and may explain the muscle hypertrophy in SOL, but not in EDL. However, the IGF-1, MGF, Myostatin, and Notch1 mRNA showed no changes in both SOL and EDL. The Delta-like1 mRNA showed no changes in SOL (CLEB: 100.7±20.3%, Control: 100.0±9.5 %), but significantly increased in EDL (CLEB: 167.3±28.0%, Control: 100.0±25.0 %; P<0.01). The Numb mRNA also showed no changes in SOL (CLEB: 104.1±19.9%, Control: 100.0±10.3 %), but significantly increased in EDL (CLEB: 131.0±20.0%, Control: 100.0± 21.5 %; P<0.05%). The increased Numb in EDL may explain the muscle hypertrophy according to progressed differentiation of myoblast. These results suggested that the hypertrophic effects of drugs should be explained in either myofibers or satellite cells, respectively. But these markers like Notch and Numb are known as the markers of progressive cancer. Therefore, we have to examine the relationship with Notch-signaling system and carcinogenic process by doping drugs. Less

盐酸克仑特罗是一种β-2肾上腺素能受体激动剂，具有强大的肌肉合成代谢作用，禁止用作运动员的兴奋剂。最近，有充分的证据表明，肌肉肥大与卫星细胞数量的增加有关，肌细胞数量成比例地增加。已经确定，Notch 1在卫星细胞中被激活，因为它们从静止状态发展到作为肌源性前体细胞的活跃增殖状态。然而，我们已经报道了Notch 1 mRNA在SOL和EDL中均未显示出变化。此外，克伦特罗对Numb（一种质膜相关的细胞质蛋白）调节卫星细胞分化的作用仍不清楚。在这项研究中，我们试图研究盐酸克伦特罗对快肌和慢肌的Numb调节系统的肥大作用。据说克伦特罗增加了MyoD作为生肌主调节剂，并可能诱导肌肉 ...更多信息肌肉湿重增加，在SOL和EDL肌肉与克伦特罗。肌细胞生成素mRNA在两种肌肉中均显示增加。SOL组MyoD mRNA表达显著增加。这可能解释了SOL肌纤维类型由慢向快转变的快缩纤维的积累，并可能解释了SOL肌肥大，但不解释EDL肌肥大。然而，IGF-1，MGF，肌肉生长抑制素和Notch 1 mRNA在SOL和EDL中均未显示出变化。δ-like 1 mRNA在SOL中无变化（CLEB：100.7± 20.3%，对照：100.0± 9.5%），但在EDL中显著增加（CLEB：167.3± 28.0%，对照：100.0± 25.0%; P<0.01）。Numb mRNA在SOL中也没有变化（CLEB：104.1± 19.9%，对照：100.0± 10.3%），但在EDL中显著增加（CLEB：131.0± 20.0%，对照：100.0± 21.5%; P<0.05%）。趾长伸肌中Numb的增加可能与成肌细胞分化的进展有关。这些结果表明，药物的肥大效应应解释在肌纤维或卫星细胞，分别。但这些标记物，如Notch和Numb，被称为进行性癌症的标记物。因此，有必要研究Notch信号系统与兴奋剂致癌过程的关系。少