PATHOPHYSIOLOGY OF CARBOHYDRATE-DEFICIET GLYCOPROTEIN SYNDROME
| Project/Area Number |
10670729
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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 |
Pediatrics
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| Research Institution | TOTTORI UNIVERSITY |
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Principal Investigator |
OHNO Kousaku DEPARTMENT OF NEUROBIOLOGY, TOTTORI UNIVERSITY, PROFESSOR, 医学部, 教授 (70112109)
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| Co-Investigator(Kenkyū-buntansha) |
HIGAKI Katsumi DEPARTMENT OF NEUROBIOLOGY, TOTTORI UNIVERSITY, LECTURER, 医学部, 助手 (90294321)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | carbohydrate-deficient glycoprotein (CDG) / sugar chain / transferrin / lysosome / b-hexosaminidase / dolichol / disialotransferrin / asialotransferrin / Carbohydrate-deficient glycoprotein / リソソーム酸素 |
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| Research Abstract |
Carbohydrate-deficient glycoprotein syndrome (CDGS) is an autosomal recessive disorders characterized by appearance of serum asparagine-N-linked glycoprotein with defective sugar chain. The basic defect of CDGS type I has been identified in the phosphomannomutase 2 gene in 1997. Abnormal glycoproteins in CDGS have been identified only in serum glycoproteins. To identify intracellular glycosylation abnormalities, we have been studied in cultured fibroblasts from three Japanese patients with CDGS type I. In this project we have studied sugar chains of lysosomal enzymes synthesized in cultured fibroblasts. We have failed to identify the abnormal fractions with defective sugar chains in several lysosomal enzymes in media and in cells. Then we have studied intrecellular processing of β-hexosaminidase and found that protein and mRNA levels of a 55-kDa mature form of the α chain. It was suggested that intracellular processing of glycoproteins including b-hexosaminidase in CDG fibroblasts might be altered. In cultured fibroblasts we have studied a pathway to form full-sized lipid linked oligosaccharide (LLO) using labeled mannose and found patient fibroblasts required six times higher concentrations of mannose to form dull-sized LLO. Various reagents restoring the LLO syn thesis in CDGS type I fibroblasts were screened and the addition of dolichol was found to be most effective to restore the formation of the full-sized LLO. These phenomena may be due to activation of dolichol phosphomannose synthase by addition of dolichol, since the level of dolichol and LLO are decreased in CDGS type I fibroblasts as described in our previous paper (J Biol Chem 272, 6868-6875, 1997).
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Report
(3 results)
Research Products
(11 results)
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[Publications] Ohkura, T., Fukushima, K., Kurisaki, A., Sagami, H., Ogura, K., Ohno, K., Harakuge, S., and Yamashita, K.: "A Partial deficiency of dehydrodolichol reduction is a cause of carbohydrate-deficient glycoprotein syndrome type I"J. Biol. Chem.. 272. 6868-6875 (1997)
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