Aminoguanidine and its pro-oxidant effects on an experimental model of protein glycation.
Recent reports show a pro-oxidant activity of aminoguanidine. Aminoguanidine is able to generate hydrogen peroxide in the presence of Cu (II). These observations have been confirmed by the present studies in that aminoguanidine is, indeed, able to generate oxidants similar in reactivity to the hydroxyl radical and is also able to fragment BSA in a Cu (II)-dependent manner. Studies on glycated bovine serum albumin show that aminoguanidine can affect a number of parameters associated with the nonenzymatic glycation of protein. This includes an ability to decrease glucose attachment and levels of protein fluorescence termed glycophore, resulting from protein glycation. Aminoguanidine also increases the generation of dicarbonyl compounds by glycated protein. All of these effects on parameters of glycation appear to be Cu (II) dependent. Further studies show that one effect of protein glycation is to decrease its susceptibility to proteolysis. The reverse is true of protein oxidation, which has previously been shown to increase the susceptibility of proteins to proteolytic digestion. Evidence is presented suggesting that aminoguanidine is able to enhance the proteolytic digestion of glycated BSA, a protein shown to be protease resistant. Our observations are discussed within the context of current concepts of protein glycation in the development of diabetic complications and aminoguanidine's potential use as a prophylactic agent in diabetes mellitus.
University of Cambridge, Department of Pathology, UK.
J T
JT
Skamarauskas
A G
AG
McKay
J V
JV
Hunt
D002918:Chymotrypsin / Q000378:metabolism; D003920:Diabetes Mellitus; D010450:Endopeptidases / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006146:Guanidines / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D010434:Pepsin A / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D006146:Guanidines; D016877:Oxidants; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D006861:Hydrogen Peroxide; D010450:Endopeptidases; D002918:Chymotrypsin; D014357:Trypsin; D010434:Pepsin A; C004479:pimagedine; D000093423:Glycated Serum Albumin