González Antonio, Granados María P, Pariente José A, Salido Ginés M
Department of Physiology, University of Extremadura, Avenida Universidad s/n, E-10071 Cáceres, Spain.
Neurochem Res. 2006 Jun;31(6):741-50. doi: 10.1007/s11064-006-9078-y. Epub 2006 Jun 23.
The effect of hydrogen peroxide (H2O2) on cytosolic free calcium concentration ([Ca2+]c) as well as its effect on glutamate secretion in rat hippocampal astrocytes have been the aim of the present research. Our results show that 100 microM H2O2 induces an increase in [Ca2+]c, that remains at an elevated level while the oxidant is present in the perfusion medium, due to its release from intracellular stores as it was observed in the absence of extracellular Ca2+, followed by a significant increase in glutamate secretion. Ca2+-mobilization in response to the oxidant could only be reduced by thapsigargin plus FCCP, indicating that the Ca2+-mobilizable pool by H2O2 includes both endoplasmic reticulum and mitochondria. We conclude that ROS in hippocampal astrocytes might contribute to an elevation of resting [Ca2+]c which, in turn, could lead to a maintained secretion of the excitatory neurotransmitter glutamate, which has been considered a situation potentially leading to neurotoxicity in the hippocampus.
本研究旨在探讨过氧化氢（H₂O₂）对大鼠海马星形胶质细胞胞质游离钙浓度（[Ca²⁺]c）的影响及其对谷氨酸分泌的影响。我们的结果表明，100微摩尔/升的H₂O₂会导致[Ca²⁺]c升高，当灌注培养基中存在氧化剂时，[Ca²⁺]c会维持在较高水平，这是由于在无细胞外Ca²⁺的情况下观察到其从细胞内储存库释放，随后谷氨酸分泌显著增加。只有毒胡萝卜素加FCCP才能减少对氧化剂的Ca²⁺动员，这表明H₂O₂可动员的Ca²⁺池包括内质网和线粒体。我们得出结论，海马星形胶质细胞中的活性氧可能导致静息[Ca²⁺]c升高，进而可能导致兴奋性神经递质谷氨酸的持续分泌，这被认为是一种可能导致海马神经毒性的情况。
