Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.
Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth.
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DOI：
10.1038/srep28693
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Parr T
中科院分区：
文献类型：
--
作者：
Brown DM;Williams H;Ryan KJ;Wilson TL;Daniel ZC;Mareko MH;Emes RD;Harris DW;Jones S;Wattis JA;Dryden IL;Hodgman TC;Brameld JM;Parr T
我们的目标是确定在给药过程中肌肉生长的新的分子机制。给生长猪(杜洛克/(长白/大白))注射莱克多巴胺(一种β-肾上腺素能激动剂；BA；饲料中20 ppm)或Reporin(重组生长激素；GH；10 mg/48 小时注射)，并与对照组(只喂饲料；不注射)进行27天的比较(1、3、7、13或27天)。利用Agilent猪转录组芯片分析了背最长肌的基因表达，并使用改进的maSigPro聚类算法识别了具有相似表达谱的基因簇。合成代谢制剂增加了屠体(p = 0.002)和肌肉重量(股外侧肌：p <； 0.001；半腱肌：p = 0.075)。骨骼肌中丝氨酸/一碳/甘氨酸生物合成途径基因(Phgdh、Psat1和Psph)和糖异生酶磷酸烯醇式丙酮酸羧基激酶-M(PCK2/PEPCK-M)的表达在BA处理期间增加，GH的表达程度较小(p <； 0.001，处理x时间交互作用)。BA处理3天(p <； 0.05)和7天(p <；PEPCK-M)的磷酸甘油脱氢酶蛋白表达增加2倍(p <；PEPCK-M)，而不用生长激素处理则增加2倍(p <； 0.01)。BA处理的猪骨骼肌中PHGDH和PEPCK-M的表达显著增加，这表明生物合成代谢途径在肌肉生长中发挥了作用。
We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20 ppm in feed) or Reporcin (recombinant growth hormone; GH; 10 mg/48 hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p = 0.002) and muscle weights (Vastus Lateralis: p < 0.001; Semitendinosus: p = 0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p < 0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p < 0.05) and 7 (p < 0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p < 0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth.