Ascorbic acid oxidation: a potential cause of the elevated severity of atherosclerosis in diabetes mellitus?
The exposure of mouse peritoneal macrophages to cholesterol linoleate-containing artificial lipoproteins can lead to intracellular ceroid accumulation. This can be used as a model to study the role of oxidation in macrophage uptake of lipoproteins containing unsaturated fatty acids, considered by many as a primary event in atherosclerotic plaque formation. Our studies show that ascorbic acid can both inhibit and promote the formation of ceroid in such a model system. The transition metal copper (Cu(II)) further elevates ceroid accumulation and EDTA, a metal chelator, inhibits it. When trace levels of transition metals are present, low concentrations of ascorbic acid can elevate ceroid formation. This pro- and antioxidant characteristic of ascorbic acid was confirmed by monitoring the generation of oxidants by various concentrations of ascorbic acid, assessed by benzoic acid hydroxylation or the fragmentation of BSA. We discuss these observations in the context of an apparent increase in ascorbic acid oxidation and elevated severity of atherosclerosis in diabetes mellitus.
Hunt
J V
JV
Department of Pathology, University of Cambridge, UK.
Bottoms
M A
MA
Mitchinson
M J
MJ
D000818:Animals; D001161:Arteriosclerosis / Q000150:complications* / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002566:Ceroid / Q000378:metabolism*; D002788:Cholesterol Esters / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D002566:Ceroid; D002788:Cholesterol Esters; D012710:Serum Albumin, Bovine; C021976:cholesteryl linoleate; D003300:Copper; D004492:Edetic Acid; D001205:Ascorbic Acid