在C2C12细胞中,β -肾上腺素能激动剂的增生性效应与纤维连接蛋白基因表达的增加有关,而与丝裂原激活的蛋白激酶调节无关。

E B Izevbigie, W G Bergen
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引用次数: 0

摘要

β -肾上腺素能激动剂(β - aa)增强骨骼肌中蛋白质的增加。这种刺激的特点是蛋白质合成增加,肌纤维蛋白基因表达增加,动物体内蛋白质降解抑制,体外肌肉细胞增殖和DNA合成增加。肌肉中β - aa与G蛋白偶联β -肾上腺素能受体(β - ar)结合时引发这些生理效应的机制或信号通路尚不清楚。利用C2C12成肌细胞测定β - ar配体结合特性、异丙肾上腺素(ISO)刺激下环AMP的合成,以及ISO对DNA合成、丝裂原活化蛋白激酶(MAPK)和纤维连接蛋白(FN)基因表达的影响。结果表明,C2C12细胞具有特异性、可饱和、高亲和力(Kd = 0.2 nM)的β - ar。foskolin和ISO使cAMP的产生增加了20倍(P
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells.

Beta-adrenergic agonists (beta-AA) enhance protein accretion in skeletal muscles. This stimulation is characterized by increased protein synthesis, increased expression of myofibrillar protein genes and a depression in protein degradation in animals, and increased proliferation and DNA synthesis in muscle cells in vitro. The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear. C2C12 myoblasts were used to determine beta-AR ligand binding characteristics, cyclic AMP synthesis in response to isoproterenol (ISO) stimulation, and effects of ISO on DNA synthesis, mitogen activated protein kinase (MAPK), and fibronectin (FN) gene expression. Results showed that C2C12 cells possess beta-AR which are specific, saturable, and of high affinity (Kd = 0.2 nM). Forskolin and ISO stimulated cAMP production by = 20-fold (P<0.001) and 17-fold (P<0.001), respectively. ISO and the cAMP analog, 8-bromo-cAMP (8-BC) stimulated DNA synthesis in proliferating cells by 150% (P<0.05) and 200% (P<0.01), respectively, without modulating MAPK activity, whereas addition of fetal bovine serum to culture resulted in a 500% increase (P<0.01) in DNA synthesis and MAPK activation. DNA synthesis in C2C12 cells treated with ISO, 8-BC, or FBS was abolished in the presence of 25 microM PD098059, an MAPK-kinase inhibitor, suggesting that an MAPK-dependent pathway is likely involved in C2C12 proliferation. During cAMP elevating agent stimulation, basal MAPK activity may be sufficient, in the presence of other putative signaling molecules, to support proliferation in these cells. ISO or 8-BC treatment increased FN mRNA by three- and seven-fold, respectively, in growing C2C12 cells implying a connection between increased DNA synthesis and FN gene expression.

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