Shimamoto Saki, Ijiri Daichi, Kawaguchi Mana, Nakashima Kazuki, Tada Osamu, Inoue Hiroki, Ohtsuka Akira
Department of Biochemical Science and Technology, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan; The United Graduate School of Agricultural Sciences, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Department of Biochemical Science and Technology, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
Comp Biochem Physiol A Mol Integr Physiol. 2017 Sep;211:1-6. doi: 10.1016/j.cbpa.2017.05.013. Epub 2017 Jun 1.
Adrenaline changes expression of the genes encoding peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), which is known as a regulator of muscle size, and atrogin-1/muscle atrophy F-box (MAFbx), which is a muscle-specific ubiquitin ligase. However, the subtype of β-adrenergic receptor (β-AR) involved in regulating these genes in skeletal muscle is not yet well defined. In this study, the effects of intraperitoneal injection of adrenaline and three β-AR selective agonists on chick skeletal muscle metabolism were examined, to evaluate the functions of β-AR subtypes. Adrenaline decreased atrogin-1/MAFbx mRNA levels accompanied by an increase in PGC-1α mRNA and protein levels. However, among the three selective agonists, only the β-AR agonist, dobutamine, increased PGC-1α mRNA and protein levels, while the β-AR agonist, clenbuterol, suppressed atrogin-1/MAFbx mRNA levels. In addition, preinjection of the β-AR antagonist, acebutolol, and the β-AR antagonist, butoxamine, inhibited the adrenaline-induced increase in PGC-1α mRNA levels and the decrease in atrogin-1/MAFbx mRNA levels, respectively. Compared with adrenaline administration, the β-AR agonist, BRL37344, decreased PGC-1α mRNA levels and increased atrogin-1/MAFbx mRNA levels. These results suggest that, in chick skeletal muscle, PGC-1α is induced via the β-AR, while atrogin-1/MAFbx is suppressed via the β-AR.
肾上腺素会改变编码过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）的基因表达，PGC-1α是已知的肌肉大小调节因子，还会改变atrogin-1/肌肉萎缩F盒（MAFbx）的基因表达，MAFbx是一种肌肉特异性泛素连接酶。然而，参与调节骨骼肌中这些基因的β-肾上腺素能受体（β-AR）亚型尚未明确界定。在本研究中，通过腹腔注射肾上腺素和三种β-AR选择性激动剂来检测其对雏鸡骨骼肌代谢的影响，以评估β-AR亚型的功能。肾上腺素降低了atrogin-1/MAFbx的mRNA水平，同时PGC-1α的mRNA和蛋白水平升高。然而，在三种选择性激动剂中，只有β-AR激动剂多巴酚丁胺增加了PGC-1α的mRNA和蛋白水平，而β-AR激动剂克伦特罗抑制了atrogin-1/MAFbx的mRNA水平。此外，预先注射β-AR拮抗剂醋丁洛尔和β-AR拮抗剂布托沙明，分别抑制了肾上腺素诱导的PGC-1α mRNA水平升高和atrogin-1/MAFbx mRNA水平降低。与给予肾上腺素相比，β-AR激动剂BRL37344降低了PGC-1α mRNA水平，增加了atrogin-1/MAFbx mRNA水平。这些结果表明，在雏鸡骨骼肌中，PGC-1α通过β-AR诱导产生，而atrogin-1/MAFbx通过β-AR受到抑制。
