| Budget Amount *help |
¥16,270,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Research Abstract |
Molecular mechanism of ATP-dependent transporters involved in lipid homeostasis in brain was investigated
1) Functional analysis of ABCA1. ABCA1 plays a major role in cholesterol homeostasis in our body and brain. However, the mechanisms is still not clear. To explore the mechanism of ABCA1-mediated HDL formation, we expressed human ABCA1 in insect Sf9 cells and purified it. Purified ABCA1 showed robust ATPase activity when reconstituted in liposomes made of synthetic phosphatidylcholine. The results suggest that the ATPase activity of ABCA1 is stimulated preferentially by phospholipids with choline head groups, phosphatidylcholine and sphingomyelin.
2) The effects of the cellular sphingomyelin level on HDL formation by ABCA1. When sphingomyelin content was reduced, apoA-I-dependent cholesterol efflux by ABCA1 increased 1.65-fold. Exogenously added sphingomyelin significantly reduced the apoA-I-dependent efflux of cholesterol.
3) Functional analysis of ABCG1. We have shown that ABCG1 mediates the efflux of not only cholesterol but also sphingomyelin (SM) and phosphatidylcholine. We examined whether it plays an important role in the ABCG1-mediated efflux of cholesterol. The results suggest that the ABCG1-mediated efflux of cholesterol and SM is dependent on the cellular SM level and distribution of cholesterol in the plasma membrane.
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