Abstract:
: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 microM) as well as 7,8-dihydroneopterin (1-1000 microM) resulted in a significant increase of percent apoptotic cells (measured by FACS analysis). Coincubation of both pteridines with the cytomix (interferon-gamma plus tumor necrosis factor-alpha) 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.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Schobersberger W,Hoffmann G,Hobisch-Hagen P,Bock G,Volkl H,Baier-Bitterlich G,Wirleitner B,Wachter H,Fuchs Ddoi
10.1016/s0014-5793(96)01194-5subject
Has Abstractpub_date
1996-11-18 00:00:00pages
263-8issue
2-3eissn
0014-5793issn
1873-3468pii
S0014-5793(96)01194-5journal_volume
397pub_type
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