PGC-1α regulates alanine metabolism in muscle cells.
PGC-1α regulates alanine metabolism in muscle cells.
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DOI：
10.1371/journal.pone.0190904
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Kamei Y
中科院分区：
文献类型：
--
作者：
Hatazawa Y;Qian K;Gong DW;Kamei Y
骨骼肌是人体中最大的器官，以蛋白质/氨基酸的形式储存能量，蛋白质/氨基酸在分解代谢条件下（如禁食）降解。丙氨酸是由骨骼肌合成和分泌的，用作肝脏中胚胎发生的底物。在禁食期间，PGC-1α（核受体的转录共激活因子）的表达在肝脏中增加，并调节肝脏的新生。在本研究中，我们观察到禁食期间骨骼肌中PGC-1α和丙氨酸氨基转移酶2（ALT 2）的mRNA表达增加。在过表达PGC-1α的C2 C12成肌细胞中，ALT 2的表达随着细胞和培养基中丙氨酸水平的增加而增加。此外，在C2 C12细胞的报告基因分析中，PGC-1α沿着核受体ERR，剂量依赖性地增强ALT 2启动子活性。在无葡萄糖的培养基中，PGC-1α和ALT 2的mRNA水平增加。内源性PGC-1α基因敲低可降低C2 C12细胞中ALT 2基因的表达水平。总之，在骨骼肌中，PGC-1α激活ALT 2基因表达，丙氨酸的产生可能在适应禁食中发挥作用。
The skeletal muscle is the largest organ in the human body, depositing energy as protein/amino acids, which are degraded in catabolic conditions such as fasting. Alanine is synthesized and secreted from the skeletal muscle that is used as substrates of gluconeogenesis in the liver. During fasting, the expression of PGC-1α, a transcriptional coactivator of nuclear receptors, is increased in the liver and regulates gluconeogenesis. In the present study, we observed increased mRNA expression of PGC-1α and alanine aminotransferase 2 (ALT2) in the skeletal muscle during fasting. In C2C12 myoblast cells overexpressing PGC-1α, ALT2 expression was increased concomitant with an increased alanine level in the cells and medium. In addition, PGC-1α, along with nuclear receptor ERR, dose-dependently enhanced the ALT2 promoter activity in reporter assay using C2C12 cells. In the absence of glucose in the culture medium, mRNA levels of PGC-1α and ALT2 increased. Endogenous PGC-1α knockdown in C2C12 cells reduced ALT2 gene expression level, induced by the no-glucose medium. Taken together, in the skeletal muscle, PGC-1α activates ALT2 gene expression, and alanine production may play roles in adaptation to fasting.
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影响因子：
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