Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.
Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
Fernanda
F
Hansen
Daniela Fraga
DF
de Souza
Simone da Luz
Sda L
Silveira
Ana Lúcia
AL
Hoefel
Júlia Bijoldo
JB
Fontoura
Ana Carolina
AC
Tramontina
Larissa Daniele
LD
Bobermin
Marina Concli
MC
Leite
Marcos Luiz Santos
ML
Perry
Carlos Alberto
CA
Gonçalves
D045744:Cell Line, Tumor; D004396:Coloring Agents; D004734:Energy Metabolism / Q000187:drug effects; D005910:Glioma / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D009499:Neutral Red; D010084:Oxidation-Reduction; D011419:Propidium / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D013869:Thiolester Hydrolases / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
D004396:Coloring Agents; D005947:Glucose; D017127:Glycation End Products, Advanced; D005998:Glycine; D019344:Lactic Acid; D007791:Lactoylglutathione Lyase; D009499:Neutral Red; D011419:Propidium; D011765:Pyruvaldehyde; D013778:Tetrazolium Salts; D013844:Thiazoles; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C022616:thiazolyl blue