1997 Fiscal Year Final Research Report Summary
Role of 3-deoxyglucosone in the pathogenesis of uremic and diabetic complications
| Project/Area Number |
08457287
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
NIWA Toshimitsu Nagoya University, School of Medicine Associate Professor, 医学部, 助教授 (20208268)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAYA Takashi Nagoya University, Research Institute of Enveronmental Medicine Research Associa, 環境医学研究所, 助手 (80262913)
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| Project Period (FY) |
1996 – 1997
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| Keywords | 3-deoxyglucosone / imidazolone / uremia / diabetes mellitus / amyloid / AGE |
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| Research Abstract |
3-Deoxyglucosone (3-DG) is a reactive intermediate of the Maillard reaction which is a nonenzymatic glycation reaction of proteins. To investigate the role of 3-DG in the pathogenesis of uremic and diabetic complications, we produced and anti-AGE antibody (AG-1) that reacted specifically with imidazolone, a novel advanced glycation end products (AGE). The imidazolone is the reaction products of the guanidino group of arginine with 3-DG.We demonstrated that amyloid tissue beta_2m is modified with imidazolone in patients with DRA.Further, we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in advanced stage of diabetic nephropathy as well as in atherosclerotic lesions of aortas. These results, taken together with a recent demonstration of increased serum 3-DG levels in uremia and diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term uremic and diabetic complications such as dialysis-related amyloidosis, and diabetic nephropathy and atherosclerosis.
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[Publications] Niwa T,Katsuzaki T,Miyazaki S,Momoi T,Akiba T,Miyazaki T,Nokura K,Hayase F,Tatemichi N,Takei Y.: "Amyloid beta2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis." Kidney Int. 51. 187-194 (1997)
Description
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