Microglial cell death induced by glycated bovine serum albumin: nitric oxide involvement.
Nonenzymatic glycation results in the formation of advanced glycation end products (AGEs) through a nonenzymatic multistep reaction of reducing sugars with proteins. AGEs have been suspected to be involved in the pathogenesis of several chronic clinical neurodegenerative complications including Alzheimer's disease, which is characterized with the activation of microglial cells in neuritic plaques. To find out the consequence of this activation on microglial cells, we treated the cultured microglial cells with different glycation levels of Bovine Serum Albumin (BSA) which were prepared in vitro. Extent of glycation of protein has been characterized during 16 weeks of incubation with glucose. Treatment of microglial cells with various levels of glycated albumin induced nitric oxide (NO) production and consequently cell death. We also tried to find out the mode of death in AGE-activated microglial cells. Altogether, our results suggest that AGE treatment causes microglia to undergo NO-mediated apoptotic and necrotic cell death in short term and long term, respectively. NO production is a consequence of iNOS expression in a JNK dependent RAGE signalling after activation of RAGE by AGE-BSA.
Khazaei
Mohammad R
MR
School of Biology, College of Science, Department of Health, Medical Sciences, University of Tehran, Tehran, Iran.
Habibi-Rezaei
Mehran
M
Karimzadeh
Fereshteh
F
Moosavi-Movahedi
Ali Akbar
AA
Sarrafnejhad
Abdo Alfattah
AA
Sabouni
Farzaneh
F
Bakhti
Mostafa
M
D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D017628:Microglia / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*; D000093423:Glycated Serum Albumin
D017304:Annexin A5; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D012709:Serum Albumin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D000093423:Glycated Serum Albumin