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: Christiane Enzinger, Barbara Wirleitner, Natalie Spöttl, Günther Böck, Dietmar Fuchs, Gabriele Baier-Bitterlich
• Journal: Neurochemistry international (Neurochem Int) Vol. 41 Issue 1 Pg. 71-8 (Jul 2002) ISSN: 0197-0186 [Print] England
• PMID: 11918974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pteridines

Topics

• Animals
• Apoptosis (drug effects)
• PC12 Cells
• Pteridines (pharmacology)
• Rats