Kleinkauf-Rocha Juliana, Bobermin Larissa Daniele, Machado Priscila de Mattos, Gonçalves Carlos-Alberto, Gottfried Carmem, Quincozes-Santos André
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Int J Dev Neurosci. 2013 May;31(3):165-70. doi: 10.1016/j.ijdevneu.2012.12.006. Epub 2012 Dec 31.
Alpha lipoic acid (LA) is a sulfhydryl compound, used as dietary supplement and to treat a variety of conditions associated to oxidative stress. Glial cells are key modulators of neuroprotection. We show here that LA modulates specific glial parameters in C6 astrocyte cell line, such as glutamate uptake, glutamine synthetase (GS) activity and glutathione content, commonly associated with the protective role of glial cells. LA (10 and 50μM) after 24h of treatment significantly decreased the formation of reactive oxygen species (ROS) and nitric oxide (NO) levels, and increased glutamate uptake (up to 20%), GS activity (25%) and GSH content (up to 40%). LA increase glutamate uptake probably by decreasing oxidizing conditions and/or by mechanism dependent of protein kinase C (PKC). In contrast, high concentrations of LA (1000μM) decreased these glial functions. Moreover, this concentration increased ROS production and NO levels. In summary, these findings show that low doses of LA were able to modulate glial functions and it appears to have remarkable therapeutic potential in neurological diseases involving oxidative stress by improving glutamatergic metabolism.
α-硫辛酸（LA）是一种巯基化合物，用作膳食补充剂并用于治疗与氧化应激相关的多种病症。神经胶质细胞是神经保护的关键调节因子。我们在此表明，LA可调节C6星形胶质细胞系中的特定神经胶质参数，例如谷氨酸摄取、谷氨酰胺合成酶（GS）活性和谷胱甘肽含量，这些通常与神经胶质细胞的保护作用相关。处理24小时后，10和50μM的LA显著降低了活性氧（ROS）的形成和一氧化氮（NO）水平，并增加了谷氨酸摄取（高达20%）、GS活性（25%）和谷胱甘肽含量（高达40%）。LA可能通过降低氧化条件和/或通过依赖蛋白激酶C（PKC）的机制来增加谷氨酸摄取。相反，高浓度的LA（1000μM）会降低这些神经胶质功能。此外，该浓度会增加ROS的产生和NO水平。总之，这些发现表明，低剂量的LA能够调节神经胶质功能，并且通过改善谷氨酸能代谢，它在涉及氧化应激的神经疾病中似乎具有显著的治疗潜力。
