| Project/Area Number |
14571104
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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 |
Metabolomics
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| Research Institution | Nagoya City University |
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Principal Investigator |
ABE Sumiko Nagoya City University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究科, 講師 (70227700)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Shinji Nagoya City University, Graduate School of Medical Sciences, Professor and Chair, 大学院・医学研究科, 教授 (10142192)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | HDL / cholesterol / ABCA1 / ABCA7 / apolipoprotein |
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| Research Abstract |
Various kinds of cell line cells were investigated for their response to lipid-free apolipoproteins to analyze the mechanism of apolipoprotein-mediated HDL generation. Major results are as follows.
1.Change in apolipoprotein-mediated HDL generation in 293 cells expressing mutant ABCA1 cDNA found in Tangier's disease Patients is not identical, indicated that the mechanism of ABCA1-dependent HDL generation has several steps.
2.There is a splicing variant (type II) cDNA of human ABCA7 and its tissue distribution and function in apo A-I-dependent lipid release is different from those of full length (type I) cDNA.
3.Human ABCA7 (type I) supports apolipoprotein-mediated HDL generation from 293 cells as well as ABCA1 dose.
4.Apolipoprotein A-I activates protein kinase C (presumably PKCα) and stabilizes ABCA1 protein in human fibroblast WI38 cells.
5.Not lipidated but dissociated form of apolipoprotein A-I is essential for HDL generation from dBcAMP-treated RAW264,mouse macrophage-like cell line, cells.
6.Verapamil and relative calcium channel blockers increases ABCA1 expression thorough LXR-independent mechanism and increases apoA-I-mediated HDL generation form dBcAMP-treated RAW264 cells.
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