Effect of increased concentration of D-glucose or L-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kappaB.
Increased adhesion of monocytes to endothelial cells has been linked to the development and progression of atherosclerosis in humans with diabetes. Previous studies have shown that increased concentration of glucose and subsequent generation of reactive oxygen species and the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) may mediate this response. However, our studies have shown that in addition to glucose, other monosaccharides, such as L-fucose, which is increased in circulation in diabetes, may also contribute to the development of diabetic complications. In these studies, we examined the effect of an increased concentration of L-fucose on monocyte adhesion to cultured bovine aorta endothelial cells. Exposing cultured bovine aorta endothelial cells to an increased concentration of either glucose or L-fucose caused a concentration-dependent increase in adhesion of monocytes. The increase in monocyte adhesion induced by glucose or L-fucose was preceded by the activation to NF-kappaB and the generation of reactive oxygen species. The combination of glucose and L-fucose at a submaximal concentration did not appear to have an additive effect on the induction of monocyte adhesion. The addition of alpha-lipoic acid partially prevented the glucose and L-fucose-induced activation of NF-kappaB, generation of reactive oxygen species, and increase in monocyte adhesion. This suggests that the effect of an increased concentration of glucose or L-fucose on monocyte adhesion to endothelial cells is at least partially due to the production oxygen-derived free radicals. Furthermore, these studies provide evidence that monosaccharides other than glucose that are increased in the circulation of humans with diabetes may contribute to vascular defects in diabetes.
Yorek
Mark A
MA
Department of Internal Medicine, Diabetes-Endocrinology Research Center and Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52246, USA.
Dunlap
Joyce A
JA
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002448:Cell Adhesion; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology*; D005643:Fucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
D017931:DNA Primers; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D005643:Fucose; D005947:Glucose