Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
Universidade Feevale, Rio Grande do Sul, 93525-075 Novo Hamburgo, RS, Brazil.
Oxid Med Cell Longev. 2017;2017:9574201. doi: 10.1155/2017/9574201. Epub 2017 Jun 8.
The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG exposure impairs primary astrocyte viability, as evaluated by different assays, and these cells respond to MG elevation by increasing glyoxalase 1 activity and glutathione levels, which improve cell viability and survival. However, C6 glioma cells have shown strong signs of resistance against MG, without significant changes in the glyoxalase system. Results for aminoguanidine coincubation support the idea that MG toxicity is mediated by glycation. We found a significant decrease in glutamate uptake by astrocytes, without changes in the expression of the major transporters. Carbenoxolone, a nonspecific inhibitor of gap junctions, prevented the cytotoxicity induced by MG in astrocyte cultures. Thus, our data reinforce the idea that astrocyte viability depends on gap junctions and that the impairment induced by MG involves glutamate excitotoxicity. The astrocyte susceptibility to MG emphasizes the importance of this compound in neurodegenerative diseases, where the neuronal damage induced by MG may be aggravated by the commitment of the cells charged with MG clearance.
星形胶质细胞功能障碍与糖尿病和其他神经退行性疾病有关。星形胶质细胞被认为是对抗高水平甲基乙二醛 (MG) 的神经保护所必需的细胞，MG 是一种来自糖酵解途径的高反应性醛。不同的测定方法评估表明，MG 暴露会损害原代星形胶质细胞的活力，而这些细胞通过增加醛糖酶 1 活性和谷胱甘肽水平来应对 MG 升高，从而提高细胞活力和存活率。然而，C6 神经胶质瘤细胞对 MG 表现出强烈的耐药迹象，糖氧还酶系统没有明显变化。氨基胍共孵育的结果支持 MG 毒性是通过糖化介导的观点。我们发现星形胶质细胞摄取谷氨酸的能力显著下降，而主要转运体的表达没有变化。非特异性缝隙连接抑制剂 carbenoxolone 可防止 MG 在星形胶质细胞培养物中诱导的细胞毒性。因此，我们的数据强化了星形胶质细胞活力依赖于缝隙连接的观点，并且 MG 诱导的损伤涉及谷氨酸兴奋性毒性。星形胶质细胞对 MG 的敏感性强调了这种化合物在神经退行性疾病中的重要性，其中 MG 诱导的神经元损伤可能因负责清除 MG 的细胞的承诺而加重。
