Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wirleitner, B; Czaputa, R; Oettl, K; Bock, G; Widner, B; Reibnegger, G; Baier, G; Fuchs, D; Baier-Bitterlich, GR.
Induction of apoptosis by 7,8-dihydroneopterin: involvement of radical formation.
Immunobiology. 2001; 203(4):629-641
Doi: 10.1016/S0171-2985(01)80012-7
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PubMed
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- Co-Autor*innen der Med Uni Graz
- Öttl Karl
- Reibnegger Gilbert
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- Abstract:
- Interferon-gamma is a cytokine released in large amounts during cell-mediated immune response. It induces the expression of proinflammatory cytokines and enhances macrophage capacity to secrete reactive oxygen intermediates and the pteridines neopterin and 7,8-dihydroneopterin. To assay the role of these pteridines in the immune system several studies were performed. Thereby, 7,8-dihydroneopterin was found to induce apoptosis in T lymphocytes. In this study we report that caspases are involved in 7,8-dihydroneopterin-mediated apoptosis in Jurkat T cells. In connection with this result we found that 7,8-dihydroneopterin can increase Fas ligand expression detected in Western blot analysis and promoter reporter assays. Antioxidants potently reduced the effect of 7,8-dihydroneopterin on Fas ligand promoter activation suggesting an involvement of oxidative stress. In further investigations, ESR-measurements were performed to evaluate the role of 7,8-dihydroneopterin in the formation of radicals. We found that the pteridine in combination with the spin trap DMPO induces the production of DMPO-OH spin adducts. This reaction was sensitive to the presence of chelated metal ions and could completely be blocked by the addition of superoxide dismutase. These data suggest that 7,8-dihydroneopterin in aqueous solution leads to the formation of .OH radicals via generation of superoxide anion. We hypothesize that an overproduction of radicals caused by high levels of 7,8-dihydroneopterin is likely to be responsible for the pro-apoptotic effects observed in cell cultures and possibly contributes to the pathogenesis of diseases involving immune activation and elevated concentrations of neopterin-derivatives.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - drug effects
- Cyclic N-Oxides - drug effects
- Electron Spin Resonance Spectroscopy - drug effects
- Fas Ligand Protein - drug effects
- Humans - drug effects
- Hydroxyl Radical - metabolism
- Interferon Type II - metabolism
- Jurkat Cells - metabolism
- Membrane Glycoproteins - metabolism
- Neopterin - analogs and derivatives
- Pteridines - pharmacology
- Reactive Oxygen Species - metabolism
- Spin Labels - metabolism
- T-Lymphocytes - cytology