Tramontina Francine, Leite Marina C, Gonçalves Daniela, Tramontina Ana Carolina, Souza Daniela F, Frizzo Juliana K, Nardin Patrícia, Gottfried Carmem, Wofchuk Susana T, Gonçalves Carlos-Alberto
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Neurochem Res. 2006 Jun;31(6):815-20. doi: 10.1007/s11064-006-9085-z. Epub 2006 Jun 23.
Several molecules have been shown to be involved in glial-neuronal communication, including S100B, an astrocyte-derived neurotrophic cytokine. Extracellular S100B protects hippocampal neurons from excitotoxic damage, whilst toxic levels of glutamate to neurons have been shown to reduce S100B secretion in astrocytes and brain slices, by an unknown mechanism. Here, we investigate which mechanisms are possibly involved in this effect in primary cultures of hippocampal astrocytes using glutamate agonists and glutamate uptake inhibitors. DCG-IV, an agonist of group II metabotropic glutamate receptors, caused a smaller decrease in S100B secretion when compared to 1 mM glutamate. D: -aspartate partially reverted the glutamate effect on S100B release and two other inhibitors, PDC and DIDS, reverted it completely. These findings suggest that S100B secretion is inversely coupled to glutamate uptake. Decrease in S100B secretion may be considered as direct excitotoxic damage, but a beneficial mechanism effect cannot be ruled out, because S100B elevation could cause an additional cell death.
已有研究表明，包括星形胶质细胞源性神经营养细胞因子S100B在内的几种分子参与了神经胶质细胞与神经元之间的通讯。细胞外的S100B可保护海马神经元免受兴奋性毒性损伤，而高浓度的谷氨酸对神经元有毒性作用，已证实其可通过未知机制减少星形胶质细胞和脑片中S100B的分泌。在此，我们使用谷氨酸激动剂和谷氨酸摄取抑制剂，研究在原代培养的海马星形胶质细胞中，哪些机制可能参与了这一效应。与1 mM谷氨酸相比，II组代谢型谷氨酸受体激动剂DCG-IV引起的S100B分泌减少幅度较小。D-天冬氨酸部分逆转了谷氨酸对S100B释放的影响，另外两种抑制剂PDC和DIDS则完全逆转了该影响。这些发现表明，S100B的分泌与谷氨酸摄取呈负相关。S100B分泌减少可能被视为直接的兴奋性毒性损伤，但有益的机制效应也不能排除，因为S100B升高可能导致额外的细胞死亡。
