Neopterin and 7,8-dihydroneopterin induce apoptosis in the rat alveolar epithelial cell line L2.

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 Lett

journal_title

FEBS letters

authors

Schobersberger W,Hoffmann G,Hobisch-Hagen P,Bock G,Volkl H,Baier-Bitterlich G,Wirleitner B,Wachter H,Fuchs D

doi

10.1016/s0014-5793(96)01194-5

subject

Has Abstract

pub_date

1996-11-18 00:00:00

pages

263-8

issue

2-3

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(96)01194-5

journal_volume

397

pub_type

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