| Project/Area Number |
15591086
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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 | Ochanomizu University (2004-2005)
The University of Tokyo (2003) |
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Principal Investigator |
SAKAKIHARA Yoichi (2004-2005) Ochanomizu University, Research center for child and adolescent development, Professor, 子ども発達教育研究センター, 教授 (10143463)
斉藤 真木子 (2003) 東京大学, 医学部附属病院, 助手 (20225733)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMORI Masao Kinki University, Faculty of sceince and tevhnology, Department of biochemistry, professor, 理工学部, 教授 (90110022)
久保田 雅也 東京大学, 医学部附属病院, 助手 (90251272)
榊原 洋一 東京大学, 医学部附属病院, 講師 (10143463)
市堰 浩 東京大学, 医学部附属病院, 助手 (20282650)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Zellweger sundrome / peroxisome / ceramide monohexoside / membrane fluifdity / Z65細胞 / プラズマローゲン / 過酸化水素 / コレステロールエステル / セレブロシド / ホスファチジルコリン / Pex5 / ZP102細胞 |
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| Research Abstract |
The study was conducted to determine the changes in the compositions and metabolism of lipids in peroxisome biogenesis disorders. In the cerebral cortex of a ZS patient, the amounts of ceramide monohexoside (CMH) and cholesterol ester (CE) increased in comparison to control levels of various ages. Although CMH accumulated with age in the white matter, absence of increase of CMH was recognized in ZS. Analysis of molecular species of PC plus PS fraction revealed significant increase of dipalmytoyl glycerophospholipids in cerebral cortex of ZS. We also analyzed lipids composition in ZP102 cells defect peroxisomes and exhibit impairments of peroxisomal β-oxidation of fatty acids and biosynthesis of plasmalogen. The concentration of free fatty acids in ZP102 cells was twice that in CHO-K1 cells, but their methyl esters and triacylglycerol in ZP102 cells were decreased in comparison to the control cells. Also, the concentration of CMH in ZP102 cells was significantly increased compared to that in the control cells, and the fatty acid molecular species, particularly the ratio of saturated and unsaturated ones, of individual lipids were different between two cell types. The rate of incorporation of [^<14>C] labeled saturated acids into sphingomyelin (SM) and CMH in ZP102 cells was higher than that in CHO-K1 cells. Lignoceric acid incorporated into cells was dominantly utilized for the synthesis of SM at 24 hr after removal of [^<14>C] lignoceric acid from the culture medium. ZP102 cells showed lower membrane mobility as compared to CHO-K1 cells. Alteration of lipid metabolism in particular enhanced metabolism of saturated fatty acids and sphingolipids may be related to the reduced membrane fluidity of ZP102 cells, which is implicated in dysfunction of membrane-linked processes in PBD
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