| Project/Area Number |
06454170
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
HORIUCHI Seikoh Kumamoto University School of Medicine, Professor, 医学部, 教授 (10117377)
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| Co-Investigator(Kenkyū-buntansha) |
ARAKI Norie Kumamoto University School of Medicine, Assistant, 医学部, 助手 (80253722)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1995: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | advanced glycation end products (AGE) / AGE receptor / macrophages / scavenger receptor / vascular smooth muscle cells / diabetic complications / aging / 老化 / グリケーション / 糖尿病 |
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| Research Abstract |
The receptor for AGE-modified proteins (AGE-receptor) has been characterized from its potential link to aging and disease processes such as diabetic complications and atherosclerosis. In the present study, we attempted to characterize the AGE-receptor of macrophages and vascular smooth muscle cells and the following results were obtained.
[1] Four AGE-binding proteins (90K,48K,28K & 18K) were purified from macrophage-derived cell line (RAW cells). N-Terminal analyzes indicated that three of them were ones already known, and 28K-protein was a novel one. The latter is being analyzed.
[2] The macrophage scavenger receptor (MSR) was already cloned by Kodama et al. CHO cells overexpressing MSR c-DNA (CHO-SRII cells) showed and enhanced endocytic uptake not only for acetyl-LDL (a ligand for MSR), but also for AGE-BSA.The endocytic uptake of AGE-BSA by these cells were effectively inhibited by acetyl-LDL.Furthermore, resident peritoneal macrophages obtained from MSR gene-knockout mice showed a marked reduction in their capacity to degrade AGE-BSA,less than 30% compared with those obtained from wild type litter mates. These data suggest that MSR plays a major role in the endocytic uptake of AGE-proteins by macrophages or macrophage-derived cells.
[3] This study was initiated by our immunological demonstration of the AGE-accumulation in smooth muscle cells-derived foam cells in the advanced stage of human atherosclerotic lesions. Smooth muscel cells (SMC) from rabbit aorta possessed a high-affinity binding site for AGE-proteins. AGE-proteins underwent endocytic uptake by SMC and induced the cell migration (chemotaxis) of these SMC.Since acetyl-LDL did not affect the endocytic uptake of AGE-proteins by these SMC nor the AGE-proteins-induced chemotaxis, it is suggested that the AGE-receptor expressed by SMC differs from MSR.The ligand blotting analysis identified a 200Kd-protein. We are now determining partial amino acid sequences.
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