2000 Fiscal Year Final Research Report Summary
Mechanism for regulation of cholesterol metabolism of astrocite in central nervous system
| Project/Area Number |
11670634
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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 |
Neurology
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| Research Institution | Nagoya City University |
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Principal Investigator |
ITO Jinichi Nagoya City University, Medical School, Associate Professor, 医学部, 助教授 (60167260)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Shinji Nagoya City University Medical School, Professor, 医学部, 教授 (10142192)
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| Project Period (FY) |
1999 – 2000
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| Keywords | astrocyte / cholesterol / HDL / caveolin1 / sphingomyelin / apoE |
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| Research Abstract |
Intercellular cholesterol transport in the brain is carried mainly by HDL, and the brain HDL is presumably generated in situ by the cellular interaction with apolipoprotein (apo) E mainly synthesized by astrocytes and with apoA-I secreted by the cells such as endothelial cells. We have studied an intracellular cholesterol transport mechanism for the release of cellular cholesterol linked to this HDL assembly system by using fetal rat brain astrocytes.
While apoA-I increased biosyntheses of cholesterol and phospholipid in the endoplasmic reticulum (ER)/Golgi only after the 120-min incubation, translocation of cholesterol and phospholipid from ER/Golgi to cytosol was stimulated by apoA-I 30 min prior to the biosynthesis stimulation. Caveolin-1 simultaneously increased in the cytosol, and lipids that appeared in the cytosol was recovered in the fraction of the density range 1.10-1.15 g/mL with caveolin 1 and cyclophilin A.Cyclosporine A, a drug that binds to cyclophilin A, suppressed the apoA-I-mediated cholesterol release, as well as the stimulation of the biosynthesis, translocation of cholesterol and appearance of cyclophilin A in the cytosol by apoA-I.These findings suggested that the translocation of cholesterol into the cytosol is related to apoA-I-mediated cholesterol release, and the system seems to depend on caveolin-1 and cyclophilin A.
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