Cardiac peroxiredoxins undergo complex modifications during cardiac oxidant stress
| Autor: | Philip Eaton, Ewald Schröder, Jonathan P. Brennan |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Antioxidant Physiology medicine.medical_treatment Immunoblotting hydrogen peroxide In Vitro Techniques 030204 cardiovascular system & hematology Peroxide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) medicine Animals Cysteine Disulfides Rats Wistar redox signaling Hydrogen peroxide 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Dose-Response Relationship Drug Myocardium Peroxiredoxins Articles Oxidants Rats PRDX3 Perfusion Oxidative Stress Cytosol chemistry Biochemistry Chromatography Gel Thiol Cardiology and Cardiovascular Medicine Oxidation-Reduction Signal Transduction |
| Zdroj: | American Journal of Physiology. Heart and Circulatory Physiology |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | Peroxiredoxins (Prdxs), a family of antioxidant and redox-signaling proteins, are plentiful within the heart; however, their cardiac functions are poorly understood. These studies were designed to characterize the complex changes in Prdxs induced by oxidant stress in rat myocardium. Hydrogen peroxide, a Prdx substrate, was used as the model oxidant pertinent to redox signaling during health and to injury at higher concentrations. Rat hearts were aerobically perfused with a broad concentration range of hydrogen peroxide by the Langendorff method, homogenized, and analyzed by immunoblotting. Heart extracts were also analyzed by size-exclusion chromatography under nondenaturing conditions. Hydrogen peroxide-induced changes in disulfide bond formation, nonreversible oxidation of cysteine (hyperoxidation), and subcellular localization were determined. Hydrogen peroxide induced an array of changes in the myocardium, including formation of disulfide bonds that were intermolecular for Prdx1, Prdx2, and Prdx3 but intramolecular within Prdx5. For Prdx1, Prdx2, and Prdx5, disulfide bond formation can be approximated to an EC50of 10–100, 1–10, and 100–1,000 μM peroxide, respectively. Hydrogen peroxide induced hyperoxidation, not just within monomeric Prdx (by SDS-PAGE), but also within Prdx disulfide dimers, and reflects a flexibility within the dimeric unit. Prdx oxidation was also associated with movement from the cytosolic to the membrane and myofilament-enriched fractions. In summary, Prdxs undergo a complex series of redox-dependent structural changes in the heart in response to oxidant challenge with its substrate hydrogen peroxide. |
| Databáze: | OpenAIRE |
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