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