Methylglyoxal and carboxyethyllysine reduce glutamate uptake and S100B secretion in the hippocampus independently of RAGE activation.
Diabetes is a metabolic disease characterized by high fasting-glucose levels. Diabetic complications have been associated with hyperglycemia and high levels of reactive compounds, such as methylglyoxal (MG) and advanced glycation endproducts (AGEs) formation derived from glucose. Diabetic patients have a higher risk of developing neurodegenerative diseases, such as Alzheimer's disease or Parkinson's disease. Herein, we examined the effect of high glucose, MG and carboxyethyllysine (CEL), a MG-derived AGE of lysine, on oxidative, metabolic and astrocyte-specific parameters in acute hippocampal slices, and investigated some of the mechanisms that could mediate these effects. Glucose, MG and CEL did not alter reactive oxygen species (ROS) formation, glucose uptake or glutamine synthetase activity. However, glutamate uptake and S100B secretion were decreased after MG and CEL exposure. RAGE activation and glycation reactions, examined by aminoguanidine and L-lysine co-incubation, did not mediate these changes. Acute MG and CEL exposure, but not glucose, were able to induce similar effects on hippocampal slices, suggesting that conditions of high glucose concentrations are primarily toxic by elevating the rates of these glycation compounds, such as MG, and by generation of protein cross-links. Alterations in the secretion of S100B and the glutamatergic activity mediated by MG and AGEs can contribute to the brain dysfunction observed in diabetic patients.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Fernanda
F
Hansen
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Cíntia Eickhoff
CE
Battú
Departamento de Biologia Celular, Embriologia e Genética, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Trindade, Florianópolis, SC, 88040-970, Brazil.
Márcio Ferreira
MF
Dutra
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Fabiana
F
Galland
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Franciane
F
Lirio
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90046-900, Brazil.
Núbia
N
Broetto
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil.
Patrícia
P
Nardin
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, 90035-003, Brazil. casg@ufrgs.br.
Carlos-Alberto
CA
Gonçalves
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D003920:Diabetes Mellitus / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006943:Hyperglycemia / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D011765:Pyruvaldehyde / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism*
C000593874:Ager protein, rat; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; D018698:Glutamic Acid; C054688:N(6)-(1-carboxyethyl)lysine; D011765:Pyruvaldehyde; D005974:Glutamate-Ammonia Ligase; D005947:Glucose; D008239:Lysine
Advanced glycation endproducts; Diabetes; Glutamate uptake; Hyperglycemia; Methylglyoxal; S100B secretion