Stimulation by glutamine and proline of HGF production in hepatic stellate cells.
Amino acids regulate cellular functions in a variety of cell types. Most notably, leucine stimulates protein production through the mammalian target of rapamycin (mTOR)-dependent signaling pathway. We investigated the effect of amino acids on hepatocyte growth factor (HGF) production. Treatment with glutamine and proline, as well as leucine, increased HGF levels in the culture medium of a rat hepatic stellate cell clone in a dose-dependent manner. Up-regulation of phosphorylation of 70 kDa ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein 1 was not apparent in the cells after treatment with glutamine or proline. When rats received injections of glutamine or proline, hepatic and circulating HGF levels increased and peaked around 12h after treatment. Glutamine and proline may have the potential to stimulate HGF production but the mechanism underlying this stimulation seems not to be through the mTOR-dependent signaling pathway.
Nishikawa
Takako
T
Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan.
Tomiya
Tomoaki
T
Ohtomo
Natsuko
N
Inoue
Yukiko
Y
Ikeda
Hitoshi
H
Tejima
Kazuaki
K
Watanabe
Naoko
N
Tanoue
Yasushi
Y
Omata
Masao
M
Fujiwara
Kenji
K
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002469:Cell Separation; D003470:Culture Media; D005973:Glutamine / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011392:Proline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism
D002352:Carrier Proteins; D003470:Culture Media; C499526:Eif4ebp1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D005973:Glutamine; D017228:Hepatocyte Growth Factor; D011392:Proline; D038762:Ribosomal Protein S6 Kinases, 70-kDa