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Glucose Induced Protein Oxidation and Macrophage Protein Metabolism - AN0412

Glucose in solution or once covalently bound to protein, can generate oxidants able to oxidise proteins, and free radical scavenging agents in a process dependent on the availability of catalytic transition metals. We wold like to elucidate such reactions further. The effects of antioxidants, metal chelators and inhibitors of development of advanced glycosylation endproducts (AGE) upon these processes will be investigated. Carbohydrate attachment, lysine derivatisation, the effect of protein histidine content, pro-oxidant and antioxidant activity, protein fragmentation and cross-linking, sulphydryl oxidation and flourescence alterations will be monitored on exposing albumins or LDL to glucose. The effect of protein oxidation upon susceptibility to enzymic proteolysis in vitro will be assessed. The uptake and degeneration of such oxidised protein by macrophages will be studied. The effect of oxidised proteins upon cellular proteolytic activity and any cytotoxic effect of oxidised protein will be monitored.
To investigate biochemical mechanisms in which oxidative reactions of glucose contribute to the elevated severity of atherosclerosis in diabetes melitus.
Time-Scale and Cost
From: 1993

To: 1996

Cost: £269,073
Contractor / Funded Organisations
University - Cambridge