Reduced pteridine derivatives induce apoptosis in PC12 cells

被引:25
作者
Enzinger, C
Wirleitner, B
Spöttl, N
Böck, G
Fuchs, D
Baier-Bitterlich, G
机构
[1] Univ Innsbruck, Ludwig Boltzmann Inst AIDS Res, Inst Med Chem & Biochem, A-6020 Innsbruck, Austria
[2] Inst Expt Pathol, A-6020 Innsbruck, Austria
关键词
neurodegeneration; apoptosis; pteridines; oxidative stress; antioxidants; MAP kinase; PC12;
D O I
10.1016/S0197-0186(01)00134-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In cerebrospinal fluid of patients with cerebral infections, elevated concentrations of the pteridine compounds neopterin and 7,8-dihydroneopterin were detected. Here, the potential of pteridines to induce apoptosis of the rat pheochromocytoma cells (PC12) was investigated. In contrast to aromatic pteridines Eke neopterin, the reduced forms 7,8-dihydroneopterin, 5,6,7,8-tetrahydrobiopterin and 7,8-dihydrobiopterin led to a significant increase of apoptotic cells. After terminal differentiation, cells were less sensitive to incubation with pteridines. A noticeable augmentation of apoptosis was observed upon incubation with 7,8-dihydroneopterin and 7,8-dihydrofolic acid. Antioxidants partly protected PC 12 cells from pteridine-induced apoptosis, suggesting the involvement of reactive oxygen intermediates, Exposure of cells to 7,8-dihydroneopterin led to activation of the mitogen-activated protein (MAP) kinase and to a lesser degree also of JUN/SAP kinase. Results implicate that high concentrations of reduced pteridines, might contribute to the pathogenesis involved in neurodegeneration. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:71 / 78
页数:8
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