1995 Fiscal Year Final Research Report Summary
Structure and Function of Receptors for Advanced Glycation End Products of the Maillard Reaction
| 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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| Keywords | advanced glycation end products (AGE) / AGE receptor / macrophages / scavenger receptor / vascular smooth muscle cells / diabetic complications / aging |
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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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[Publications] Araki, N., Higashi, T., Mori, T., Shibayama, R., Kawabe, Y., Kodama, T., Takahashi, K., Shichiri, M.and Horiuchi, S.: "Macrophage scavenger receptor mediates the endocytic uptake of advanced glycation end-products of the Maillard reaction." Eur.J.Biochem.230. 408-415 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kume, S., Takeya, M., Mori, T., Araki, N., Suzuki, H., Horiuchi, S., Kodama, T., Miyauchi, Y.and Takahasji, K.: "Immunohistrochemical and ultrastrucutral detection of advanced glycation end products in atherosclerotic lesions of human aorta using a novel specific monoclonal antibody." Am.J.Pathol. 147. 654-667 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Makino, H., Shikata, K., Hironaka, K., Kushiro, M., Yamasaki, Y., Sugimoto, H., Ota, Z., Araki, N.and Horiuchi, S.: "Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephrophathy." Kidney International. 48. 517-526 (1995)
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[Publications] Saishoji, T., Higashi, T., Ikeda, K., Jinnouchi, Y., Sano, H., Ogawa, M.and Horiuchi, S.: "Advanced glycation end products stimulate plasminogen activator activity via GM-CSF in RAW264.7 cells." Biochem.Biophys.Res.Commun.217. 278-285 (1995)
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「研究成果報告書概要(欧文)」より
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[Publications] Miyata, T., Taneda, S., Kawai, R., Otani, K., Horiuchi, S., Hara, M., Maeda, K.and Monnier, V.M.: "Identification of pentosidine as a native structure for advanced glycation end products in b2-microglobulin forming amyloid fibrils in patients with dialysis-related amyloidosis." Proc, Natl.Acad.Sci.USA.(in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Horiuchi, S., Higashi, T., Ikeda, K., Saishoji, T., Jinnouchi, Y., Sano, H., Shibayama, R., Sakamoto, T.& Araki, N.: "Advanced glycation end products (AGE) and their recognition by macrophage and macrophage-derived ells." Diabetes. (in press).
Description
「研究成果報告書概要(欧文)」より
