Neopterin derivatives together with cyclic guanosine monophosphate induce c‐fos gene expression

FEBS Letters

Fuchs, Dietmar¹  Grunicke, Hans H.¹  Schubert, Christian¹  Werner-Felmayer, Gabriele¹  Überall, Florian¹  Wachter, Helmut¹ 

[1] Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl Strasse 3, A-6020 Innsbruck, Austria

关键词: Neopterin;    7;    8-Dihydroneopterin;    Cyclic GMP;    c-fos;    NIH3T3 fibroblast;   

DOI  :  10.1016/0014-5793(94)00899-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have previously shown that neopterin enhances hydrogen peroxide and chloramine T activity in a luminol-dependent chemiluminescence assay and strengthens toxicity of these agents against bacteria at slightly alkaline pH (pH 7.5), while 7,8-dihydroneopterin was shown to be a scavenger independent of the pH value. Besides various oxidants, phenolic antioxidants were shown to specifically induce expression of the c-fos and c-jun mRNAs. Using an inducible cfosCAT reporter transactivation system we studied the function of the pteridine derivatives on c-fos transactivation. For the first time, we demonstrate that neopterin and 7,8-dihydroneopterin, particularly together with cyclic guanosine monophosphate, induce c-fos gene expression. In humans, interferon-γ induces the release of neopterin and 7,8-dihydroneopterin and also the synthesis of nitric oxide radical which in turn stimulate the formation of cGMP. Thus, in certain situations all three substances, namely neopterin, 7,8-dihydroneopterin and cGMP, may be present locally and even in the circulation at the same time. Based on our findings this constellation would significantly enhance the risk of c-fos gene expression and therefore promote tumour growth and development.

【 授权许可】

Unknown