Reversible Oxidative Modifications in Myoglobin and Functional Implications
Autor: | Amanda M. Eccardt, Mark H. Mannino, Jonathan S. Fisher, Blythe E. Janowiak, Fahu He, David C. Wood, Rishi S. Patel |
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Rok vydání: | 2020 |
Předmět: |
inorganic chemicals
0301 basic medicine Hemeprotein Physiology Clinical Biochemistry peroxidase Peptide Protein aggregation Biochemistry Article protein aggregation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Molecular Biology Heme chemistry.chemical_classification biology lcsh:RM1-950 Tryptophan Cell Biology Ascorbic acid dityrosine lcsh:Therapeutics. Pharmacology 030104 developmental biology ditryptophan chemistry Myoglobin myoglobin Biophysics biology.protein 030217 neurology & neurosurgery Peroxidase |
Zdroj: | Antioxidants Volume 9 Issue 6 Antioxidants, Vol 9, Iss 549, p 549 (2020) |
ISSN: | 2076-3921 |
Popis: | Myoglobin (Mb), an oxygen-binding heme protein highly expressed in heart and skeletal muscle, has been shown to undergo oxidative modifications on both an inter- and intramolecular level when exposed to hydrogen peroxide (H2O2) in vitro. Here, we show that exposure to H2O2 increases the peroxidase activity of Mb. Reaction of Mb with H2O2 causes covalent binding of heme to the Mb protein (Mb-X), corresponding to an increase in peroxidase activity when ascorbic acid is the reducing co-substrate. Treatment of H2O2-reacted Mb with ascorbic acid reverses the Mb-X crosslink. Reaction with H2O2 causes Mb to form dimers, trimers, and larger molecular weight Mb aggregates, and treatment with ascorbic acid regenerates Mb monomers. Reaction of Mb with H2O2 causes formation of dityrosine crosslinks, though the labile nature of the crosslinks broken by treatment with ascorbic acid suggests that the reversible aggregation of Mb is mediated by crosslinks other than dityrosine. Disappearance of a peptide containing a tryptophan residue when Mb is treated with H2O2 and the peptide&rsquo s reappearance after subsequent treatment with ascorbic acid suggest that tryptophan side chains might participate in the labile crosslinking. Taken together, these data suggest that while exposure to H2O2 causes Mb-X formation, increases Mb peroxidase activity, and causes Mb aggregation, these oxidative modifications are reversible by treatment with ascorbic acid. A caveat is that future studies should demonstrate that these and other in vitro findings regarding properties of Mb have relevance in the intracellular milieu, especially in regard to actual concentrations of metMb, H2O2, and ascorbate that would be found in vivo. |
Databáze: | OpenAIRE |
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