Neurochem Int 2002 Jul;41(1):71-8
Institute for Medical Chemistry and Biochemistry, Ludwig Boltzmann Institute for AIDS Research, University of Innsbruck, Fritz Pregl Street 3, 6020 Innsbruck, Austria.
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 like 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 PC12 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.