Hatazawa Yukino, Qian Kun, Gong Da-Wei, Kamei Yasutomi
Laboratory of Molecular Nutrition, Graduate School of Life and Environmental Science, Kyoto Prefectural University, Kyoto, Japan.
Japan Society for the Promotion of Science, Tokyo, Japan.
PLoS One. 2018 Jan 9;13(1):e0190904. doi: 10.1371/journal.pone.0190904. eCollection 2018.
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.
骨骼肌是人体最大的器官，以蛋白质/氨基酸形式储存能量，在诸如禁食等分解代谢状态下会被降解。丙氨酸由骨骼肌合成并分泌，在肝脏中用作糖异生的底物。禁食期间，肝脏中核受体的转录共激活因子PGC-1α的表达增加，并调节糖异生。在本研究中，我们观察到禁食期间骨骼肌中PGC-1α和丙氨酸转氨酶2（ALT2）的mRNA表达增加。在过表达PGC-1α的C2C12成肌细胞中，ALT2表达增加，同时细胞和培养基中的丙氨酸水平升高。此外，在使用C2C12细胞的报告基因检测中，PGC-1α与核受体ERR一起剂量依赖性地增强了ALT2启动子活性。在培养基中缺乏葡萄糖时，PGC-1α和ALT2的mRNA水平升高。C2C12细胞中内源性PGC-1α敲低降低了由无葡萄糖培养基诱导的ALT2基因表达水平。综上所述，在骨骼肌中，PGC-1α激活ALT2基因表达，丙氨酸生成可能在适应禁食中发挥作用。
