St-Amand J, Okamura K, Matsumoto K, Shimizu S, Sogawa Y
Saga Research Institute, Otsuka Pharmaceutical Company, Higashi-sefuri, Kanzaki, Saga, 842-0195, Japan.
FASEB J. 2001 Mar;15(3):684-92. doi: 10.1096/fj.00-0150com.
To elucidate the molecular basis of muscle atrophy, we have performed the serial analysis of gene expression (SAGE) method with control and immobilized muscles of 10 rats. The genes that expressed >0.5% in muscle are involved in the following three functions: 1) contraction (troponin I, C and T; myosin light chain 1-3; actin; tropomyosin; and parvalbumin), 2) energy metabolism (cytochrome c oxidase I and III, creatine kinase, glyceraldehyde-3-phosphate-dehydrogenase, phosphoglycerate mutase, ATPase 6, and aldolase A), and 3) housekeeping (lens epithelial protein). Muscle atrophy appears to be caused by changes in mRNA levels of specific regulators of proteolysis, protein synthesis, and contractile apparatus assembling, such as polyubiquitin, elongation factor 2, and nebulin. Immobilization has produced a decrease more than threefold in gene expression of enzymes involved in energy metabolism, especially ATPase, cytochrome c oxidase, NADH dehydrogenase, and protein phosphatase 1. Differential gene expressions of selenoprotein W and uroporphyrinogen decarboxylase, which can be involved in oxidative stress, were also observed. Other genes with various functions, such as cholesterol metabolism and growth factors, were also differentially expressed. Moreover, novel genes regulated by immobilization were discovered. Thus, the current study allows a better understanding of global muscle characteristics and the molecular mechanisms of sedentarity and sarcopenia.
为阐明肌肉萎缩的分子基础，我们采用基因表达序列分析（SAGE）方法，对10只大鼠的对照肌肉和固定肌肉进行了研究。在肌肉中表达量>0.5%的基因涉及以下三种功能：1）收缩（肌钙蛋白I、C和T；肌球蛋白轻链1 - 3；肌动蛋白；原肌球蛋白；和小清蛋白），2）能量代谢（细胞色素c氧化酶I和III、肌酸激酶、甘油醛-3-磷酸脱氢酶、磷酸甘油酸变位酶、ATP酶6和醛缩酶A），以及3）管家功能（晶状体上皮蛋白）。肌肉萎缩似乎是由蛋白水解、蛋白质合成和收缩装置组装的特定调节因子的mRNA水平变化引起的，如多聚泛素、延伸因子2和伴肌动蛋白。固定导致参与能量代谢的酶的基因表达下降了三倍多，尤其是ATP酶、细胞色素c氧化酶、NADH脱氢酶和蛋白磷酸酶1。还观察到可能参与氧化应激的硒蛋白W和尿卟啉原脱羧酶的差异基因表达。其他具有各种功能的基因，如胆固醇代谢和生长因子，也有差异表达。此外，还发现了受固定调节的新基因。因此，本研究有助于更好地了解整体肌肉特征以及久坐不动和肌肉减少症的分子机制。
