1988 Fiscal Year Final Research Report Summary
Non-enzymatic glycosylation of proteins in biological sytem and its physiological significance in aging process.
| Project/Area Number |
62570136
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
HORIUCHI Seikoh Department of Biochemistry, Kumamoto University Medical School., 医学部, 講師 (10117377)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Nonenzymatic glycosylation / Maillard reaction / Aging process / Diabetic complications / Receptor |
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| Research Abstract |
Nonenzymatic glycosylation of proteins with glucose named the Maillard reaction leads, through a Schiff base adduct and Amadori rearrangement products, to advanced glycosylation end product (AGE) with fluorescence, brown color and cross-linked property. Protein modification in vivo by the Maillard reaction. Particularly age-products, is believed to play an important role in deabetic complications or aging processes, although nothing is known about a chemical structure(s) of AGE-proteins. In the present project, we elucidated the biological property of AGE-products. An attempt was also made to determine the chemical structure of AGE-product(s). Following results were obtained.
1. AGE-proteins such as AGE-albumin and AGE-hemoglobin underwent receptor-mediated endocytosis by macrophages or macrophage-derived cells, including rat sinusoidal liver cells, rat and murine peritoneal macrophages and human monocyte macrophages. The receptor was found to be identical to a scavenger receptor for aldehyde-modified proteins which had been discovered by us in 1986.
2. Cerami et al. claimed that 2-(2-furoyl)-4(5)-(furanyl)-1H-imidazole (FFI) was involved in the recepter recognition. However, our experiment using synthesized FFI derivatives clearly showed that this was not the case.
3. Determination by the radioimmunoassay using an anti-FFI antibody and by high performance liquid chromatography demonstrated that FFI was in fact an artifact generated after acid hydrolysis of AGE-proteins and subsequent reaction with ammonia, evidence against in vivo presence of FFI.
4. The major fluorescent compound was isolated from AGE-l-lysine derivatives. Immunological analyses indicated that this fluorescent compound did occur to age-proteins. Its precise chemical structure is being determined.
The above results taken together suggest that a structure in common among AGE-proteins might be crucial to the biological recognition by the scavenger receptor.
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