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增殖刺激活性对肌肉培养物中细胞内蛋白水解的抑制作用。增殖刺激活性与胰岛素对蛋白水解、蛋白质合成、氨基酸摄取及糖转运影响的比较。

Inhibition of intracellular proteolysis in muscle cultures by multiplication-stimulating activity. Comparison of effects of multiplication-stimulating activity and insulin on proteolysis, protein synthesis, amino acid uptake, and sugar transport.

作者信息

Janeczko R A, Etlinger J D

出版信息

J Biol Chem. 1984 May 25;259(10):6292-7.

PMID:6373754
Abstract

The effects of the insulin-like growth factor, multiplication-stimulating activity (MSA), on chick myotube cultures were investigated. In serum-free media, MSA at levels reported to be present in fetal serum (5 ng/ml) significantly inhibited overall rates of protein degradation and stimulated protein synthesis and amino acid uptake. Half-maximal effects on protein degradation (-30%), synthesis (+25%), and amino acid uptake (+50%) occurred at approximately 0.05 micrograms/ml. In contrast, 10(2)-10(3)-fold higher concentrations (5 micrograms/ml) were required to stimulate transport of the glucose analog 2-deoxyglucose. The results indicate that MSA is an effective anabolic agent regulating protein metabolism and amino acid uptake, but not sugar transport in these cells. Parallel studies conducted with insulin demonstrated similar size effects on protein metabolism and amino acid uptake in serum-free media. However, unlike MSA, insulin levels (10(-2) units/ml) well in excess of its normal physiological range were required to produce significant effects. In addition, the relative sensitivity of sugar transport with respect to protein metabolic effects differed for insulin and MSA. Thus, 2-deoxyglucose transport was approximately 10 times more sensitive to insulin than protein synthesis, proteolysis, or amino acid uptake in contrast to MSA where the reverse was true. However, despite the relatively higher sensitivity of sugar transport to insulin, supraphysiological levels (10(-3) units/ml) of this hormone were still required for significant stimulation. These results suggest a generally low insulin sensitivity in cultured chick myotubes relative to adult tissues. In contrast, the effects of MSA are consistent with a possible role of this or similar factors in regulating growth and development of embryonic muscle.

摘要

研究了胰岛素样生长因子即促增殖活性物质(MSA)对鸡肌管培养物的影响。在无血清培养基中,据报道胎儿血清中存在的水平(5纳克/毫升)的MSA显著抑制蛋白质降解的总体速率,并刺激蛋白质合成和氨基酸摄取。对蛋白质降解(-30%)、合成(+25%)和氨基酸摄取(+50%)产生半数最大效应时的浓度约为0.05微克/毫升。相比之下,刺激葡萄糖类似物2-脱氧葡萄糖的转运需要浓度高10²-10³倍(5微克/毫升)。结果表明,MSA是一种有效的合成代谢剂,可调节这些细胞中的蛋白质代谢和氨基酸摄取,但不调节糖转运。用胰岛素进行的平行研究表明,在无血清培养基中对蛋白质代谢和氨基酸摄取有类似程度的影响。然而,与MSA不同,需要远超其正常生理范围的胰岛素水平(10⁻²单位/毫升)才能产生显著影响。此外,胰岛素和MSA在糖转运相对于蛋白质代谢效应的相对敏感性方面存在差异。因此,与MSA情况相反,2-脱氧葡萄糖转运对胰岛素的敏感性比对蛋白质合成、蛋白水解或氨基酸摄取的敏感性高约10倍,在MSA中情况则相反。然而,尽管糖转运对胰岛素的敏感性相对较高,但仍需要超生理水平(10⁻³单位/毫升)的这种激素才能产生显著刺激。这些结果表明,相对于成年组织,培养的鸡肌管中的胰岛素敏感性普遍较低。相比之下,MSA的作用与该因子或类似因子在调节胚胎肌肉生长和发育中的可能作用一致。

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