Cytotoxicity of advanced glycation endproducts in human micro- and astroglial cell lines depends on the degree of protein glycation.
Advanced glycation endproducts (AGEs) arise from the reaction of sugars with side chains and the N-terminus of proteins and are thought to be involved in the pathogenesis of several diseases by inducing oxidative stress, inflammation and cell death presumably mediated through activation of the receptor of AGE (RAGE). To address the question whether the cell damaging effect of AGE depends on the degree of its protein glycation, differential modified AGEs derived from incubating human serum albumin with increasing concentrations of methyl glyoxal were tested on cell viability, reactive oxygen species (ROS) formation, intracellular ATP levels, and activation of caspases 3/7 in two human glial cell lines, which were used as a model for human glia cells. All AGEs tested, regardless of their degree of modification, were found to induce ROS formation in both microglial (CHME-5) and astroglial cells (U373 MG), while only highly modified AGEs were able to decrease the cell viability and to induce apoptosis. This indicates that apoptotic events may be involved in the change of physiological parameters.
Bigl
Katrin
K
Interdisciplinary Centre of Clinical Research (IZKF), Faculty of Medicine, University of Leipzig, Inselstr. 22, 04103, Leipzig, Germany. katrin.bigl@yahoo.de
Gaunitz
Frank
F
Schmitt
Annett
A
Rothemund
Sven
S
Schliebs
Reinhard
R
Münch
Gerald
G
Arendt
Thomas
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017127:Glycation End Products, Advanced; D011506:Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D053148:Caspase 3; D053179:Caspase 7