Toxicity of sugars and identification of markers for pathophysiology in citrin deficiency leading to development of novel therapeutics
Project/Area Number |
21591337
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Kumamoto University (2011) Tokushima Bunri University (2009-2010) |
Principal Investigator |
SAHEKI Takeyori 熊本大学, 生命資源研究・支援センター, 特任教授 (10056070)
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Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Keiko 鹿児島大学, 大学院・医歯学総合研究科, 准教授 (70108869)
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Project Period (FY) |
2009 – 2011
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Project Status |
Completed (Fiscal Year 2011)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | シトリン / 成人発症II型シトルリン血症(CTLN2) / 新生児肝内胆汁うっ滞症(NICCD) / マウスモデル / 糖質毒性 / メタボローム解析 / アスパラギン酸・グルタミン酸ミトコンドリア膜輸送体 / glycerol-3-phosphate / シトリン欠損症 / エタノール / グリセロール / glycerol3-phosphate / NICCD / glycerol 3-hosphate |
Research Abstract |
We have established a model mouse of citrin deficiency causing neonatal intrahepatic cholestasis(NICCD) at neonatal period and adult-onset type II citrullinemia(CTLN2) at adult age. We showed that administration of sugars to the mice caused deterioration such as hyperammonemia. From the metabolomics analysis, we found that administration of sugars induced a marked increase in hepatic glycerol-3-phosphate(G3P), which is useful as a biomarker for citrin deficiency. We found that dietary change from high protein to low protein induced a decreased body weight, mimicking growth retardation or skinniness in the disease and that addition of substance such as protein, amino acids, pyruvate and medium-chain triglyceride to the low-protein diet increased food intake and body weight.
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Genotypic and phenotypic features of citrin deficiency : five-year experience in a Chinese pediatric center2011
Author(s)
Song YZ, Deng M, Chen FP, Wen F, Guo L, Cao SL, Gong J, Xu H, Jiang GY, Zhong L, Kobayashi K, Saheki T, Wang ZN
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Journal Title
Int J Mol Med
Volume: 28(1)
Pages: 33-40
Related Report
Peer Reviewed
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[Journal Article] Genotypic and phenotypic features of citrin deficiency : Five-year experience in a Chinese pediatric center.2011
Author(s)
Song YZ, Deng M, Chen FP, Wen F, Guo L, Cao SL, Gong J, Xu H, Jiang GY, Zhong L, Kobayashi K, Saheki T, Wang ZN.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Sustaining hypercitrullinemia, hypercholesterolemia and augmented oxidative stress in Japanese children with aspartate/glutamate carrier isoform 2-citrin-deficiency even during the silent period2009
Author(s)
Nagasaka H, Okano Y, Tsukahara H, Shigematsu Y, Momoi T, Yorifuji J, Miida T, Ohura T, Kobayashi K, Saheki T, Hirano K, Takayanagi M, Yorifuji T.
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Journal Title
Mol Genet Metab. 97
Pages: 21-26
Related Report
Peer Reviewed
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[Journal Article] Neonatal intrahepatic cholestasis caused by citrin deficiency : clinical and laboratory investigation of 13 subjects in mainland of China2009
Author(s)
Song YZ, Li BX, Chen FP, Liu SR, Sheng JS, Ushikai M, Zhang CH, Zhang T, Wang ZN, Kobayashi K, Saheki T, Zheng XY.
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Journal Title
Dig Liver Dis. 41
Pages: 683-689
Related Report
Peer Reviewed
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[Journal Article] Living donor liver transplantation for type II citrullinemia from a heterozygous donor2009
Author(s)
Hirai I, Kimura W, Suto K, Fzjimoto H, Watanabe T, Fuse A, Kobayashi K, Iijima M, Saheki T, Nakatsuka T, Sugawara Y, Makuuchi M.
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Journal Title
Hepatogastroenterology 55
Pages: 2211-22
Related Report
Peer Reviewed
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[Journal Article] Neonatal intrahepatic cholestasis caused by citrin deficiency(NICCD)as a cause of liver disease in infants in the UK.2009
Author(s)
Hutchin T, Preece MA, Hendriksz C, Chakrapani A, McClelland V, Okumura F, Song YZ, Iijima M, Kobayashi K, Saheki T, McKiernan P, Baumann U.
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Journal Title
J Inherit Metab Dis. On line
Related Report
Peer Reviewed
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