Vitamin E, Ascorbate, Glutathione, Glutathicne Disulfide, and Enzymes of Glutathione Metabolism in Cultures of Chick Astrocytes and Neurons: Evidence that Astrocytes Play an Important Role in Antioxidative Processes in the Brain
Vitamin E, Ascorbate, Glutathione, Glutathicne Disulfide, and Enzymes of Glutathione Metabolism in Cultures of Chick Astrocytes and Neurons: Evidence that Astrocytes Play an Important Role in Antioxidative Processes in the Brain
复制标题
DOI：
10.1046/j.1471-4159.1994.62010045.x
复制
发表时间：
1994-01
影响因子：
4.7
通讯作者：
T. Makar;M. Nedergaard;A. Preuss;A. Gelbard;A. S. Perumal;Arthur J. L. Cooper
中科院分区：
文献类型：
--
作者：
T. Makar;M. Nedergaard;A. Preuss;A. Gelbard;A. S. Perumal;Arthur J. L. Cooper
摘要：在鸡星形胶质细胞和神经元的14天培养物中测量GSH、GSSG、维生素E和抗坏血酸盐，并与相当年龄的鸡胚前脑中的水平进行比较。还测量了参与GSH代谢的酶的活性。这些包括-γ-谷氨酰半胱氨酸合成酶、GSH合成酶、γ-谷氨酰环转移酶、γ-谷氨酰转肽酶、谷胱甘肽转移酶（GST）、GSH过氧化物酶和GSSG还原酶。发现培养的神经元中脂溶性维生素E的浓度与前脑中的浓度相当。另一方面，星形胶质细胞中维生素E的浓度在培养的星形胶质细胞中显著大于神经元中，表明星形胶质细胞能够比神经元更广泛地积累外源性维生素E。培养神经元细胞膜中主要脂肪酸的浓度高于星形胶质细胞。在培养的细胞中没有检测到抗坏血酸，尽管鸡前脑中含有可观水平的这种抗氧化剂。GSH，总谷胱甘肽（即，培养的星形胶质细胞中GSH和GSSG活性明显高于神经元。培养的星形胶质细胞中γ-谷氨酰半胱氨酸合成酶活性高于培养的神经元。GSH还原酶和GSH过氧化物酶活性在培养的星形胶质细胞和神经元中大致相当。培养的星形胶质细胞中高水平的GSH和GST似乎反映了体内的情况。这些数据表明，星形胶质细胞对活性氧（和潜在的有毒异生物质）具有抵抗力，并可能在大脑中发挥保护作用。由于GSH代谢酶通常在培养的星形胶质细胞和神经元中有很好的代表性，因此这些细胞可能非常适合作为体外操纵神经组织中GSH水平的探针。培养的星形胶质细胞和神经元应适合于研究各种代谢损伤对GSH系统的影响。这些研究可能为设计治疗策略以对抗氧化和外源性压力提供见解。
Abstract: GSH, GSSG, vitamin E, and ascorbate were measured in 14‐day cultures of chick astrocytes and neurons and compared with levels in the forebrains of chick embryos of comparable age. Activities of enzymes involved in GSH metabolism were also measured. These included ‐γ‐glutamylcysteine synthetase, GSH synthetase, γ‐glutamyl cyclotransferase, γ‐glutamyltranspeptidase, glutathione transferase (GST), GSH peroxidase, and GSSG reductase. The concentration of lipid‐soluble vitamin E in the cultured neurons was found to be comparable with that in the forebrain. On the other hand, the concentration of vitamin E in the astrocytes was significantly greater in the cultured astrocytes than in the neurons, suggesting that the astrocytes are able to accumulate exogenous vitamin E more extensively than neurons. The concentrations of major fatty acids were higher in the cell membranes of cultured neurons than those in the astrocytes. Ascorbate was not detected in cultured cells although the chick forebrains contained appreciable levels of this antioxidant. GSH, total glutathione (i.e., GSH and GSSG), and GST activity were much higher in cultured astrocytes than in neurons. γ‐Glutamylcysteine synthetase activity was higher in the cultured astrocytes than in the cultured neurons. GSH reductase and GSH peroxidase activities were roughly comparable in cultured astrocytes and neurons. The high levels of GSH and GST in cultured astrocytes appears to reflect the situation in vivo. The data suggest that astrocytes are resistant to reactive oxygen species (and potentially toxic xenobiotics) and may play a protective role in the brain. Because enzymes of GSH metabolism are generally well represented in cultured astrocytes and neurons these cells may be ideally suited as probes for manipulating GSH levels in neural tissues in vitro. Cultured astrocytes and neurons should be amenable to the study of the effects of various metabolic insults on the GSH system. Such studies may provide insights into the design of therapeutic strategies to combat oxidative and xenobiotic stresses.