Spöttl N, Wirleitner B, Böck G, Widner B, Fuchs D, Baier-Bitterlich G
Institut for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Immunobiology. 2000 Jan;201(3-4):478-91. doi: 10.1016/S0171-2985(00)80100-X.
Elevated concentrations of the pteridine compound neopterin, usually accompanied by 7,8-dihydroneopterin were found in cerebrospinal fluids of patients with neurodegenerative diseases and central nervous system infections. Here, the potential of pteridines to induce apoptosis of the human neuronal cell line (NT2) was investigated. Reduced neopterin, biopterin- and folate derivatives led to a time-dependent increase of apoptosis of cells. In contrast, non-reduced pteridines did not significantly alter cell survival. After differentiation of neuronal precursor cells to neurons and astrocyte-like cells, similar effects were detected. Antioxidants partly protected NT2 from pteridines-induced apoptosis, suggesting the involvement of reactive oxygen intermediates. In vitro experiments using dichlorofluorescin-diacetate further indicated a direct formation of reactive oxygen species in cells. Results implicate that high concentrations of reduced pteridines, might contribute to the loss of neuronal cells in neurodegenerative diseases.
在神经退行性疾病和中枢神经系统感染患者的脑脊液中发现，蝶啶化合物新蝶呤浓度升高，通常还伴有7,8 - 二氢新蝶呤。在此，研究了蝶啶诱导人神经母细胞瘤细胞系（NT2）凋亡的可能性。还原型新蝶呤、生物蝶呤和叶酸衍生物导致细胞凋亡随时间增加。相比之下，非还原型蝶啶对细胞存活没有显著影响。神经前体细胞分化为神经元和星形胶质样细胞后，也检测到类似的效应。抗氧化剂部分保护NT2细胞免受蝶啶诱导的凋亡，提示活性氧中间体参与其中。使用二氯荧光素二乙酸酯的体外实验进一步表明细胞中直接形成了活性氧。结果表明，高浓度的还原型蝶啶可能导致神经退行性疾病中神经元细胞的丧失。
