title: Reduced pteridine derivatives induce apoptosis in PC12 cells.
abstract: 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.
authors.affiliation: Institute for Medical Chemistry and Biochemistry, Ludwig Boltzmann Institute for AIDS Research, University of Innsbruck, Fritz Pregl Street 3, 6020 Innsbruck, Austria.
authors.forename: Christiane
authors.initials: C
authors.lastname: Enzinger
authors.forename: Barbara
authors.initials: B
authors.lastname: Wirleitner
authors.forename: Natalie
authors.initials: N
authors.lastname: Spöttl
authors.forename: Günther
authors.initials: G
authors.lastname: Böck
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baier-Bitterlich
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016716:PC12 Cells; D011621:Pteridines / Q000494:pharmacology*; D051381:Rats
chemical_list: D011621:Pteridines