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Neopterin and 7,8‐dihydroneopterin induce apoptosis in the rat alveolar epithelial cell line L2
Author(s) -
Schobersberger Wolfgang,
Hoffmann Georg,
Hobisch-Hagen Petra,
Böck Günther,
Völkl Harald,
Baier-Bitterlich Gabriele,
Wirleitner Barbara,
Wachter Helmut,
Fuchs Dietmar
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(96)01194-5
Subject(s) - neopterin , nitric oxide , apoptosis , nitric oxide synthase , alveolar macrophage , programmed cell death , biopterin , chemistry , biochemistry , biology , pharmacology , microbiology and biotechnology , immunology , macrophage , endocrinology , tetrahydrobiopterin , in vitro
The neopterin derivatives, neopterin and 7,8‐dihydroneopterin, modulate the cellular oxidant‐antioxidant balance as well as the expression of the inducible nitric oxide synthase (iNOS) gene. Since apoptosis can be induced by reactive oxygen intermediates and nitric oxide (NO) we investigated whether these neopterin derivatives induce apoptotic cell death. As model we selected the rat alveolar epithelial cell line L2. 24 h incubation of neopterin (1–1000 μM) as well as 7,8‐dihydroneopterin (1–1000 μM) resulted in a significant increase of percent apoptotic cells (measured by FACS analysis). Coincubation of both pteridines with the cytomix (interferon‐γ plus tumor necrosis factor‐α) led to a significantly higher apoptosis than the cytomix alone. In contrast to the cytomix, no iNOS gene expression and no NO release could be detected after incubation with neopterin or 7,8‐dihydroneopterin. We conclude that neopterin and 7,8‐dihydroneopterin are per se inducers of apoptosis which is not mediated by nitric oxide. This may be of importance in inflammatory pulmonary diseases associated with an activation of the cellular immune system.