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ß-肾上腺素信号在骨骼肌生长、发育和再生中的新作用。

Novel role for ß-adrenergic signalling in skeletal muscle growth, development and regeneration.

机构信息

Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Parkville, Vic., Australia.

出版信息

Clin Exp Pharmacol Physiol. 2010 Mar;37(3):397-401. doi: 10.1111/j.1440-1681.2009.05312.x. Epub 2009 Sep 28.

Abstract
  1. In adult mammals, skeletal muscle mass is maintained through a precise balance of protein synthesis and protein degradation, whereas during development cellular (not protein) turnover predominates. When protein balance is shifted towards synthesis, skeletal muscle hypertrophy ensues. In contrast, increased protein degradation leads to skeletal muscle atrophy. Insulin-like growth factor (IGF)-I is among the best documented of the growth factors and regulates skeletal muscle mass by increasing protein synthesis and decreasing protein degradation. However, an IGF-I-independent growth pathway has been identified that involves the activation of beta-adrenoceptors and subsequent skeletal muscle growth, development and hypertrophy. 2. Although the importance of beta-adrenergic signalling in the heart has been well documented and continues to receive significant attention, it is only more recently that we have started to appreciate the importance of this signalling pathway in skeletal muscle structure and function. Studies have identified an important role for beta-adrenoceptors in myogenesis and work from our laboratory has identified a novel role for beta-adrenoceptors in regulating skeletal muscle regeneration after myotoxic injury. In addition, new data suggest that beta-adrenoceptors are markedly upregulated during differentiation of C2C12 cells. 3. It is now clear that beta-adrenoceptors play an important role in regulating skeletal muscle structure and function. Importantly, a clearer understanding of the pathways regulating skeletal muscle mass may lead to the identification of novel therapeutic targets for the treatment of muscle wasting disorders, including sarcopenia, cancer cachexia and the muscular dystrophies.
摘要
  1. 在成年哺乳动物中,骨骼肌质量通过蛋白质合成和蛋白质降解的精确平衡来维持,而在发育过程中,细胞(而非蛋白质)更新占主导地位。当蛋白质平衡向合成方向移动时,骨骼肌就会发生肥大。相反,蛋白质降解增加会导致骨骼肌萎缩。胰岛素样生长因子 (IGF)-I 是最有文献记载的生长因子之一,通过增加蛋白质合成和减少蛋白质降解来调节骨骼肌质量。然而,已经确定了一种 IGF-I 独立的生长途径,该途径涉及β-肾上腺素受体的激活,随后是骨骼肌的生长、发育和肥大。

  2. 虽然β-肾上腺素能信号在心脏中的重要性已经得到很好的证明,并继续受到广泛关注,但直到最近我们才开始认识到这种信号通路在骨骼肌结构和功能中的重要性。研究已经确定了β-肾上腺素受体在成肌发生中的重要作用,我们实验室的工作已经确定了β-肾上腺素受体在调节肌肉毒性损伤后骨骼肌再生中的新作用。此外,新数据表明,β-肾上腺素受体在 C2C12 细胞的分化过程中明显上调。

  3. 现在很清楚,β-肾上腺素受体在调节骨骼肌结构和功能方面起着重要作用。重要的是,对调节骨骼肌质量的途径有更清晰的认识,可能会导致发现治疗肌肉消耗疾病(包括肌肉减少症、癌症恶病质和肌肉营养不良症)的新治疗靶点。

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