Scientific reports, 2016-03, Vol.6 (1), p.23071, Article 23071
2016
Details
- Autor(en) / Beteiligte
- Titel
- Mitochondrial Thioredoxin System as a Modulator of Cyclophilin D Redox State
- Ist Teil von
- Scientific reports, 2016-03, Vol.6 (1), p.23071, Article 23071
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2016
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The mitochondrial thioredoxin system (NADPH, thioredoxin reductase, thioredoxin) is a major redox regulator. Here we have investigated the redox correlation between this system and the mitochondrial enzyme cyclophilin D. The peptidyl prolyl cis-trans isomerase activity of cyclophilin D was stimulated by the thioredoxin system, while it was decreased by cyclosporin A and the thioredoxin reductase inhibitor auranofin. The redox state of cyclophilin D, thioredoxin 1 and 2 and peroxiredoxin 3 was measured in isolated rat heart mitochondria and in tumor cell lines (CEM-R and HeLa) by redox Western blot analysis upon inhibition of thioredoxin reductase with auranofin, arsenic trioxide, 1-chloro-2,4-dinitrobenzene or after treatment with hydrogen peroxide. A concomitant oxidation of thioredoxin, peroxiredoxin and cyclophilin D was observed, suggesting a redox communication between the thioredoxin system and cyclophilin. This correlation was further confirmed by i) co-immunoprecipitation assay of cyclophilin D with thioredoxin 2 and peroxiredoxin 3, ii) molecular modeling and iii) depleting thioredoxin reductase by siRNA. We conclude that the mitochondrial thioredoxin system controls the redox state of cyclophilin D which, in turn, may act as a regulator of several processes including ROS production and pro-apoptotic factors release.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/srep23071Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4791683
- Format
- –
- Schlagworte
- 1-Chloro-2,4-dinitrobenzene, Animals, Apoptosis, Arsenic, Arsenic trioxide, Auranofin - pharmacology, Blotting, Western, Cell Line, Tumor, Cyclophilins - antagonists & inhibitors, Cyclophilins - chemistry, Cyclophilins - metabolism, Cyclosporin A, Cyclosporine - pharmacology, Dinitrobenzene, HeLa Cells, Humans, Hydrogen peroxide, Hydrogen Peroxide - metabolism, Hydrogen Peroxide - pharmacology, Immunoprecipitation, Mitochondria, Mitochondria, Heart - genetics, Mitochondria, Heart - metabolism, Models, Molecular, Molecular modelling, NADP, Oxidants - metabolism, Oxidants - pharmacology, Oxidation, Oxidation-Reduction - drug effects, Peptidyl-Prolyl Isomerase F, Peroxiredoxin, Peroxiredoxin III - chemistry, Peroxiredoxin III - metabolism, Protein Binding - drug effects, Protein Domains, Rats, Wistar, Reactive oxygen species, Reactive Oxygen Species - metabolism, Redox properties, Reductase, RNA Interference, Rodents, siRNA, Thioredoxin, Thioredoxin 2, Thioredoxin Reductase 2 - antagonists & inhibitors, Thioredoxin Reductase 2 - genetics, Thioredoxin Reductase 2 - metabolism, Thioredoxins - chemistry, Thioredoxins - metabolism, Tumor cell lines