| Project/Area Number |
12671120
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Nagoya City University |
|---|
Principal Investigator |
ABE Sumiko Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (70227700)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Shinji Nagoya City University Medical School, Professor, 医学部, 教授 (10142192)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | HDL / cholesterol / ABCA1 / apolipoprotein / apolipoprotein / cholesterol / ABCAl |
|---|
| 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.
After preincubation of RAW 264, a murine monocytic leukemia cell line, with dBcAMP induced specific binding of apolipoprotein AI (apo A-I) to the cells and apoA-I-mediated HDL formation with cellular lipids, neither of which was detected in the absence of dBcAMP. Abca1 mRNA and protein were both detected in the dBcAMP-untreated cells, and the dBcAMP treatment enhanced their expression about 10 fold. The pharmacological inhibitory profile for lipid efflux by the compounds reported as inhibitors of anion transport mediated by ABCA1 protein was different from that for anion transport.
HDL was formed by interaction with apoA-I and THP・1, a human monocytic leukemia cell line. However, cholesterol incorporation into HDL was only observed after differentiation of the cells by PMA. ABCA1 mRNA and protein were almost undetectable in undifferentiated cells but induced by PMA treatment.
Neither ABCA1 expression nor apoA-I-mediated lipid release was detected in 293 cells derived from human embryonic kidney. Specific binding of apo A-I was detected in stable transformants of 293 with ABCA1 cDNA. ApoA-I-mediated phospholipid release was observed in the cells with low and high level ABCA1 expression. Cholesterol release was only detected in the cells with high level ABCA1.
These data indicated that ABCA1 protein may be essential, but not sufficient for cholesterol assembly to HDL generated by apolipoproteins.
|
