| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Jiro Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90199373)
SAWAI Toshio Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90351808)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Amino acids, such as glutamine, are reported to have the effects on protecting the disruption of intestinal barrier as the cause of liver fibrosis or multiple organ failure under the condition of intestinal failure or burn injury. We investigated the effects of amino acids, which is reported as the nutrients, such as the energy source of intestine, precursor of nucleotides, on the signaling with regards to protein biosynthesis in rat intestinal epihelial cell, IEC6 cell. In IEC6 cell, downstream signaling events of mammalian target of rapamycin(mTOR), including the activity of p70^<s6k> and phosphorylation of eukaryotic initiation factor 4E-binding protein 1, were dependent on amino acid concentration in the culture media, whereas other growth-related protein kinases, such as Akt,cdk2,p90^<rsk>, were not p70^<s6k> activity decreased within 15 min after deprivation of amino acids and became undetectable within 30 min ; levels remained undetectable throughout the time course. Additionally, supplementation of amino acids increased p70^^<s6k> activity within 15 min, and the activity reached a plateau level within 60 min. Asparagine is most effective for activation of p70^<s6k>, and glutamine is not effective for activation of p70^<s6k>. Deprivation of asparagine suppressed the growth of IEC6 cells. Asparaginase converts asparagine and glutamine to aspartate and glutamate, respectively, and causes rapid depletion of asparagine and glutamine. Asparaginase also suppressed the growth of IEC6 cells. Asparagine is not included in the solution of intravenous hyperalimentation. It is supposed that, in addition to glutamine, asparagine may have the important effects on the protein synthesis in intestine just after major surgery or burn injury, at least within 30 minutes and 6 hours, to keep the activity of p70^<s6k> and 4E-binding protein 1.
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