Artikel
Silver ions induce oxidative stress and intracellular zinc release in human skin fibroblasts
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Autoren
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Christoph Viktor Suschek
- Universitätsklinikum der RWTH-Aachen, Klinik für Plastische Chirurgie, Hand- und Verbrennungschirurgie, Aachen, Deutschland
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Klaus-D. Kröncke
- Heinrich-Heine-Universität Düsseldorf, Institute of Biochemistry and Molecular Biology I, Düsseldorf, Deutschland
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Meike Münchow
- Universitätsklinikum der RWTH-Aachen, Klinik für Plastische Chirurgie, Hand- und Verbrennungschirurgie, Aachen, Deutschland
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Elvis Pirev
- Heinrich-Heine-Universität Düsseldorf, Institute of Biochemistry and Molecular Biology I, Düsseldorf, Deutschland
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Florian Heßner
- Universitätsklinikum der RWTH-Aachen, Klinik für Plastische Chirurgie, Hand- und Verbrennungschirurgie, Aachen, Deutschland
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Ahmed Bozkurt
- Universitätsklinikum Aachen, RWTH, Klinik für Plastische Chirurgie, Hand- und Verbrennungschirurgie, Aachen, Deutschland
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Peter Uciechowski
- Universitätsklinikum der RWTH-Aachen, Institute of Immunology, Medical Faculty, Aachen, Deutschland
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Norbert Pallua
- Universitätsklinikum der RWTH Aachen, Klinik für Plastische Chirurgie, Hand- und Verbrennungschirurgie, Aachen, Deutschland
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Miriam M. Cortese-Krott
- Heinrich-Heine-Universität Düsseldorf, Department of Internal Medicine B, Cardiovascular Research Laboratory, Düsseldorf, Deutschland
| Veröffentlicht: | 17. Mai 2010 |
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Gliederung
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Introduction: As a consequence of increasing bacterial resistance to antibiotics there has been a renewed interest in other antimicrobial agents such as silver compounds, particular in the managing of skin infections, burns and chronic ulcers. The aim of this study was to investigate whether Ag affects the oxidative status and/or the zinc homeostasis of human skin fibroblasts, especially whether the toxicity of silver ions, in analogy to other transition metal ions, depends on pro-oxidant effects.
Materials and methods: Cell viability was measured by neutral red staining. The production of reactive oxygen species in human skin fibroblasts was detected by the red fluorescent probe MitoSOX or by the green fluorescent probe DCF. Cellular zinc homeostasis was characterized by Zn2 -specific fluorophore zinquin. Effects of Ag on the expression of MT and the transcription factor were characterized by real-time RT-PCR and western blot.
Results: We treated human skin fibroblasts with concentrations of AgNO3 not affecting cell proliferation, mitochondrial activity, or cell viability and found that Ag strongly increases the production of reactive oxygen species, including superoxide anion radicals. These effects correspond to a strong decrease in intracellular reduced glutathione and to an increased susceptibility to H2O2-induced cell death. In addition, AgNO3 down-regulates the expression of antioxidant genes such as the transcription factor Nrf2 and its target gene glutamate-cyteine ligase catalytic subunit. Furthermore Ag induces a transient intracellular zinc release, and increases the mRNA and protein expression of the zinc-binding protein metallothionein via activating the metal responsive transcription factor-1, as verified by RNA interference.
Conclusion: We show for the first time that Ag induces oxidative stress and affects intracellular zinc homeostasis in human skin fibroblasts. The understanding of the mechanism involved in silver toxicity might contribute to new strategies for managing the therapy of skin infections.
