1998 Fiscal Year Final Research Report Summary
Elucidation of Protein Glycation Mechanism and Development of Pharmaceuticals Preventing Diabetes Complications
| Project/Area Number |
08457596
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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 |
Physical pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
KINOSHITA Toshio Kitasato University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (70053816)
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| Co-Investigator(Kenkyū-buntansha) |
HANAI Toshihiko International Institute of Technological Analysis, Health Reseach foundation, Se, 主任研究員
ITOH Hiroko Kitasato University, School of Pharmaceutical Sciences, Assistant Professor, 薬学部, 助手 (30223176)
NIMURA Noriyuki Kitasato University, School of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (50118832)
KUBO Hiroaki Kitasato University, School of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (40050570)
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| Project Period (FY) |
1996 – 1998
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| Keywords | deabetes complication / glycated albumin / methylguanidine / active oxygen / cytochrome c / N-glycosylation / diabetic nephropathy |
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| Research Abstract |
The mechanism of protein glycation was elucidated to give a clue to prevent the glycosidation of proteins. An assay method for Amadori moiety in proteins was also established. Application of this method revealed that cytochrome c is effective for the elimination of Amadori moiety. In addition, the elimination of active oxygen was shown to prevent diabetic nephropathy and its deterioration.
1. Investigation on the properties of glycated albumin and the mechanism of glycation.
1・1 Propeties of glycated albumin The change in the propeties of albumin on glycation was found to affect the binding between warfarin and serum albumin.
1・2 Examination of protein glycation mechanism Accerelation of N-glycosylation, which is the first step of protein glycation in blood, by hydroxyl groups on sugar molecule was inspected.The configurations of aglycons were identical to those of C-3 hydroxyl groups of sugars. This fact suggests that C-3 hydroxyl groups are involved in the structure of the reaction inte
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rmediates.The glycation of proteins may proceed by way of such intermediates.
2. Estabishment of a method to estimate the glycation degree of albumin and the elimination of active oxygen generated from glycated albumin.
2・1 Assay method to estimate the glycation degree of serum albumin Glycated albumin was found to generate strong luminescence on reaction with lucigenin substantiating the generation of active oxygen from glycated albumin. This reaction was applied to the flow-injection analysis estimating the glycation degree of serum albumin.
2・2 Elimination of active oxygen generated from glycated albumin The substance eliminating the Amadori compound was searched utilizing the assay method mentioned above to show that cytochrome c is effective.
3. Developement of Fully automated analyser for serum guanidino compounds and its application to the investigation on the influence of active oxygen on the pathology of chronic renalfailure. Methylguanidine (MG), which increase in the sera of diabetic nephropathy, one of the diabetes complications, is regarded as the indicator of active oxygen. An automated system for the analysis of guanidino compounds was developed providing direct injection of serum. Application of this system to the analysis of pathology suggested that the interval between hemodialysis can be reduced for the patients showing low MG level. Less
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