Upregulation of oxidative stress markers in human microvascular endothelial cells by complexes of serum albumin and digestion products of glycated casein.
The extent of absorption of dietary advanced glycation end products (AGEs) is not fully known. The possible physiological impact of these absorbed components on inflammatory processes has been studied little and was the aim of this investigation. Aqueous solutions of bovine casein and glucose were heated at 95 degrees C for 5 h to give AGE-casein (AGE-Cas). Simulated stomach and small intestine digestion of AGE-Cas and dialysis (molecular mass cutoff of membrane = 1 kDa) resulted in a low molecular mass (LMM) fraction of digestion products, which was used to prepare bovine serum albumin (BSA)-LMM-AGE-Cas complexes. Stimulation of human microvascular endothelial cells with BSA-LMM-AGE-Cas complexes significantly increased mRNA expression of the receptor of AGE (RAGE), galectin-3 (AGE-R3), tumor necrosis factor alpha, and a marker of the mitogen-activated protein kinase pathway (MAPK-1), as well as p65NF-kappaB activation. Cells treated with LMM digestion products of AGE-Cas significantly increased AGE-R3 mRNA expression. Intracellular reactive oxygen species production increased significantly in cells challenged with BSA-LMM-AGE-Cas and LMM-AGE-Cas. In conclusion, in an in vitro cell system, digested dietary AGEs complexed with serum albumin play a role in the regulation of RAGE and downstream inflammatory pathways. AGE-R3 may protect against these effects.
Deo
Permal
P
Human Nutrition and Health Group, School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland.
Glenn
Josephine V
JV
Powell
Lesley A
LA
Stitt
Alan W
AW
Ames
Jennifer M
JM
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D002417:Cattle; D002461:Cell Line, Transformed; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D037502:Galectin 3 / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D015415:Biomarkers; D002364:Caseins; D037502:Galectin 3; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha