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

FEBS Letters

Schobersberger, Wolfgang⁴  Wirleitner, Barbara⁵  Fuchs, Dietmar⁵  Hoffmann, Georg¹  Böck, Günther³  Hobisch-Hagen, Petra⁴  Baier-Bitterlich, Gabriele⁵  Völkl, Harald²  Wachter, Helmut⁵ 

[1] Institute of Physiology I, University of Bonn, Nussallee 11, D-53115 Bonn, Germany;Institute of Physiology, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria;Institute for Experimental Pathology, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria;Division for General and Surgical Intensive Care Medicine, Clinic for Anaesthesia and General Intensive Care Medicine, University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria;Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz Pregl Strasse 3, A-6020 Innsbruck, Austria

关键词: Neopterin;    7;    8-Dihydroneopterin;    Apoptosis;    Nitric oxide;    Reactive oxygen intermediate;    Alveolar epithelial cell L2;   

DOI  :  10.1016/S0014-5793(96)01194-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown