Date
2018Journal
PLoS ONEPublisher
Public Library of ScienceType
Article
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Show full item recordAbstract
he 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.Keyword
AlanineAlanine Transaminase
Animals
Cell LineFasting
Gene Expression Regulation
Liver
MiceMice, Inbred C57BL
Muscle, Skeletal
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Promoter Regions, Genetic
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040245015&doi=10.1371%2fjournal.pone.0190904&partnerID=40&md5=dd614656d29c36ba08d463e0b256ad7c; http://hdl.handle.net/10713/9039ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0190904
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