Approach to the promotion of liver regeneration by amino acid-dependent control of signaling
| Project/Area Number |
17591362
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Hyogo College of Medicine |
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Principal Investigator |
IIBOSHI Yasuhiko Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (10340994)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAI Toshio Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90351808)
HIRANO Tadamichi Hyogo College of Medicine, Faculty of Medicine, Research Associate, 医学部, 助手 (90340968)
YAMANAKA Junichi Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90289083)
IIMURO Yuji Hyogo College of Medicine, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30252018)
FUJIMOTO Jiro Hyogo College of Medicine, Faculty of Medicine, Professor, 医学部, 教授 (90199373)
田附 裕子 兵庫医科大学, 医学部, 助手 (10397698)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Amino acid / Signaling / Liver regeneration |
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| Research Abstract |
Regarding protein synthesis, amino acids have been thought to be substrates of protein neutritionally. The purpose of this study is to reveal the pharmacological roles, that is, the influence of amino acids on the signaling associated with protein synthesis. The activation of this pathway enable us to increase the liver regeneration and the resectable liver volume. In our study, the amino acid which effectively regulates this signaling pathway was a non-essential amino acid, asparagine in the experiment of cultured hepatocytes. We already reported that L-asparaginase inhibits the rapamycin-targeted signaling pathway, p70 S6 kinase and eukaryotic initiation factor 4E-binding protein 1. p70 S6 kinase activates ribosome biogenesis and suppression of 4E-binding protein 1 by rapamycin induces apoptosis in the cell without p53. L-Asparaginase converts asparagine (Asn) to aspartate, and causes rapid depletion of Asn in the cells. Mouse hepatocellular carcinoma cell Hepal, human hepatocellular carcinoma cell HepG2, and rat small intestinal cell IEC6 as control, were incubated in the several concentration of L-aparaginase solution for 3 days. Hepa1 and HepG2 showed the apoptosis of cells and dose-dependent depression of cell-growth by L-aparaginase, while IEC6 cells recovered from the depression of cell-growth and the apoptosis was not recognized in the IEC6 cells. It is suggested that depletion of Asn may be a critical factor for cell growth and apoptosis of hepatocellular cells. Clinically there is no Asn in the solution of hyperalimentation. Early enteral nutrition may be important for liver regeneration. In our in vivo study, 70%hepatectomy of rat induced the depletion of plasma arginine (Arg) and arginase induced the regeneration of the liver. It was supposed that the depletion of Arg has some effects on the liver regeneration. Clinically it is supposed that early supplementation of Arg after liver resection improve the protein synthesis in the liver.
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Report
(3 results)
Research Products
(18 results)
