Schobersberger W, Hoffmann G, Hobisch-Hagen P, Bock G, Volkl H, Baier-Bitterlich G, Wirleitner B, Wachter H, Fuchs D
Division for General and Surgical Intensive Care Medicine, Clinic for Anaesthesia and General Intensive Care Medicine, University of Innsbruck, Austria.
FEBS Lett. 1996 Nov 18;397(2-3):263-8. doi: 10.1016/s0014-5793(96)01194-5.
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.
新蝶呤衍生物，即新蝶呤和7,8 - 二氢新蝶呤，可调节细胞的氧化还原平衡以及诱导型一氧化氮合酶（iNOS）基因的表达。由于凋亡可由活性氧中间体和一氧化氮（NO）诱导，我们研究了这些新蝶呤衍生物是否会诱导凋亡性细胞死亡。我们选择大鼠肺泡上皮细胞系L2作为模型。用新蝶呤（1 - 1000微摩尔）以及7,8 - 二氢新蝶呤（1 - 1000微摩尔）孵育24小时，导致凋亡细胞百分比显著增加（通过流式细胞术分析测定）。两种蝶啶与细胞混合液（干扰素 - γ加肿瘤坏死因子 - α）共同孵育导致的凋亡显著高于单独使用细胞混合液。与细胞混合液不同，用新蝶呤或7,8 - 二氢新蝶呤孵育后未检测到iNOS基因表达和NO释放。我们得出结论，新蝶呤和7,8 - 二氢新蝶呤本身就是凋亡诱导剂，且这种诱导并非由一氧化氮介导。这在与细胞免疫系统激活相关的炎症性肺部疾病中可能具有重要意义。
