Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase
| Autor: | Jany Vassy, Frédéric Garban, Joao Freitas, I. Emerit, Paulo Filipe, Arlette Levy |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Erythrocytes
Neutrophils Monocytes Flow cytometry Superoxide dismutase Lipid peroxidation chemistry.chemical_compound Superoxides Extracellular medicine Animals Humans Inosine Triphosphate Cells Cultured Skin chemistry.chemical_classification Microscopy Confocal Multidisciplinary biology medicine.diagnostic_test Superoxide Dismutase Superoxide Cytochrome c Antimutagenic Agents Fibroblasts Biological Sciences Flow Cytometry Molecular biology Enzyme chemistry biology.protein Cattle Tumor necrosis factor alpha Fluorescein-5-isothiocyanate Mutagens |
| Zdroj: | Proceedings of the National Academy of Sciences. 93:12799-12804 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.93.23.12799 |
| Popis: | Superoxide-mediated clastogenesis is characteristic for various chronic inflammatory diseases with autoimmune reactions and probably plays a role in radiation-induced clastogenesis and in the congenital breakage syndromes. It is consistently prevented by exogenous superoxide dismutase (SOD), but not by heat-inactivated SOD, indicating that the anticlastogenic effect is related to the catalytic function of the enzyme. Increased superoxide production by activated monocytes/macrophages is followed by release of more long-lived metabolites, so-called clastogenic factors, which contain lipid peroxidation products, unusual nucleotides of inosine, and cytokines such as tumor necrosis factor α. Since these components are not only clastogenic, but can stimulate further superoxide production by monocytes and neutrophils, the genotoxic effects are self-sustaining. It is shown here that anticlastogenic effects of exogenous SOD are preserved despite extensive washing of the cells and removal of all extracellular SOD. Using flow cytometry and confocal laser microscopy, rapid adherence of the fluorescently labeled enzyme to the cell surface could be observed with slow uptake into the cell during the following hours. The degree of labeling was concentration and time dependent. It was most important for monocytes, compared with lymphocytes, neutrophils, and fibroblasts. The cytochrome c assay showed significantly diminished O 2 − production by monocytes, pretreated with SOD and washed thereafter. The preferential and rapid binding of SOD to monocytes may be of importance not only for the superoxide-mediated genotoxic effects, described above, but also from a therapeutic standpoint. It can explain the observation that beneficial effects of injected SOD lasted for weeks and months despite rapid clearance of the enzyme from the blood stream according to pharmacodynamic studies. |
| Databáze: | OpenAIRE |
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