Degradation of glycated bovine serum albumin in microglial cells.
Glycated protein products are formed upon binding of sugars to lysine and arginine residues and have been shown to accumulate during aging and in pathologies such as Alzheimer disease and diabetes. Often these glycated proteins are transformed into advanced glycation end products (AGEs) by a series of intramolecular rearrangements. In the study presented here we tested the ability of microglial cells to degrade BSA-AGE formed by glycation reactions of bovine serum albumin (BSA) with glucose and fructose. Microglial cells are able to degrade BSA-AGEs to a certain degree by proteasomal and lysosomal pathways. However, the proteasome and lysosomal proteases are severely inhibited by cross-linked BSA-AGEs. BSA-AGEs are furthermore able to activate microglial cells. This activation is accompanied by an enhanced degradation of BSA-AGE. Therefore, we conclude that microglial cells are able to degrade glycated proteins, although cross-linked protein-AGEs have an inhibitory effect on proteolytic systems in microglial cells.
Kroto Research Institute and Centre for Nanoscience and Technology, North Campus, Sheffield University, Sheffield, UK.
Alexandra
A
Stolzing
Rebecca
R
Widmer
Tobias
T
Jung
Peter
P
Voss
Tilman
T
Grune
D000818:Animals; D002403:Cathepsins / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage; D005947:Glucose / Q000008:administration & dosage; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D016177:Macrophage-1 Antigen; D004676:Myelin Basic Protein; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D005632:Fructose; D009569:Nitric Oxide; D002403:Cathepsins; D046988:Proteasome Endopeptidase Complex; D005947:Glucose; D000093423:Glycated Serum Albumin