Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2012 Dec;27(4):531-9. doi: 10.1007/s11011-012-9329-3. Epub 2012 Jul 18.
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.
甲基乙二醛是一种二羰基化合物，在生理条件下通过酶和非酶反应产生。它可以导致细胞毒性，主要与晚期糖基化终产物（AGEs）的形成有关。甲基乙二醛和 AGEs 参与神经退行性疾病（ND）的发病机制，在这些情况下，可导致能量代谢受损。星形胶质细胞在大脑代谢和适当的星形胶质细胞功能中发挥关键作用，星形胶质细胞的存活和功能对神经元的存活和功能至关重要。然而，只有少数研究评估了甲基乙二醛对星形胶质细胞的影响。本研究旨在评估甲基乙二醛暴露对 C6 神经胶质瘤细胞葡萄糖、甘氨酸和乳酸代谢的短期（1 和 3 h）和长期（24 h）影响，以及研究糖氧醛酸酶系统和 AGEs 的形成。在 1 h 时，葡萄糖摄取和葡萄糖氧化为 CO2 增加，在 3 h 时，葡萄糖转化为脂质增加。此外，在 1 h 时，甘氨酸氧化为 CO2 和甘氨酸转化为脂质增加，而在 1 和 3 h 时，甘氨酸掺入蛋白质减少。甲基乙二醛在 24 h 内降低了糖氧醛酸酶 I 和 II 的活性并增加了 AGEs 的含量。甲基乙二醛暴露并没有改变乳酸的氧化和乳酸水平。这些数据表明，甲基乙二醛可能损害葡萄糖代谢，并影响糖氧醛酸酶的活性。在甲基乙二醛暴露增加的时期，这些变化可能会加剧，导致细胞内甲基乙二醛和 AGEs 的进一步增加，从而触发和/或加重 ND。
