Myoglobin-Induced Oxidative Damage: Evidence for Radical Transfer from Oxidized Myoglobin to Other Proteins and Antioxidants

Irwin, Jennifer A.; Østdal, Henrik; Davies, Michael J.

doi:10.1006/abbi.1998.0987

Cited by 92 publications

(87 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The decay of the g ϳ 2.036 signal and the subsequent broadening of the g ϳ 2.011 signal were also observed for horse heart Mb and the human C110A variant; however, the signal at g ϳ 2.036 did not reappear in either case, even after 30 min of incubation at 77 K (data not shown). The latter observation is consistent with that described for the decay of Trp-OO ⅐ in horse heart Mb (38).…”

Section: Reactive Thiol Content Of Recombinant and Native Proteins-supporting

confidence: 92%

Reaction of Human Myoglobin and H2O2

Witting¹,

Douglas²,

Mauk³

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

The human myoglobin (Mb) sequence is similar to other mammalian Mb sequences, except for a unique cysteine at position 110. Reaction of wild-type recombinant human Mb, the C110A variant of human Mb, or horse heart Mb with H 2 O 2 (protein/H 2 O 2 ‫؍‬ 1:1.2 mol/mol) resulted in formation of tryptophan peroxyl (Trp-OO ⅐ ) and tyrosine phenoxyl radicals as detected by EPR spectroscopy at 77 K. For wild-type human Mb, a second radical (g ϳ 2.036) was detected after decay of Trp-OO ⅐ that was not observed for the C110A variant or horse heart Mb. When the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was included in the reaction mixture at protein/DMPO ratios <1:10 mol/mol, a DMPO adduct exhibiting broad absorptions was detected. Hyperfine couplings of this radical indicated a DMPO-thiyl radical. Incubation of wild-type human Mb with thiol-blocking reagents prior to reaction with peroxide inhibited DMPO adduct formation, whereas at protein/DMPO ratios >1:25 mol/mol, DMPO-tyrosyl radical adducts were detected. Mass spectrometry of wild-type human Mb following reaction with H 2 O 2 demonstrated the formation of a homodimer (mass of 34,107 ؎ 5 atomic mass units) sensitive to reducing conditions. The human Mb C110A variant afforded no dimer under identical conditions. Together, these data indicate that reaction of wild-type human Mb and H 2 O 2 differs from the corresponding reaction of other myoglobin species by formation of thiyl radicals that lead to a homodimer through intermolecular disulfide bond formation.

show abstract

Section: Reactive Thiol Content Of Recombinant and Native Proteins-supporting

confidence: 92%

Reaction of Human Myoglobin and H2O2

Witting¹,

Douglas²,

Mauk³

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Based on previous studies, it is proposed that L-Trp initially reacts with the porphyrin radical of compound I (32,69) to produce a neutral tryptophanyl radical, which may form after rapid deprotonation of a tryptophanyl radical cation (75,76). It is also plausible that the initial reaction involves the reaction of L-Trp with an IDO protein radical (77). Upon formation, the neutral tryptophanyl radical is known to react with O 2 to form a peroxyl radical (75,77,78), which upon forming a hydroperoxide can rearrange via yet to be characterized chemistry into N-formylkynurenine that hydrolyzes into kynurenine (79,80).…”

Section: Discussionmentioning

confidence: 99%

“…It is also plausible that the initial reaction involves the reaction of L-Trp with an IDO protein radical (77). Upon formation, the neutral tryptophanyl radical is known to react with O 2 to form a peroxyl radical (75,77,78), which upon forming a hydroperoxide can rearrange via yet to be characterized chemistry into N-formylkynurenine that hydrolyzes into kynurenine (79,80). Further evidence for compound I-mediated oxidation of L-Trp is the observation that tempol and ascorbate both inhibited H 2 O 2 -induced oxidation of the amino acid by IDO (Fig.…”

Section: Discussionmentioning

confidence: 99%

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Freewan

Rees

Plaza

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Certain heme proteins exhibit a pseudo-peroxidase activity that alters their function. Results: H 2 O 2 engages the peroxidase activity of indoleamine 2,3-dioxygenase (IDO) to oxidatively inactivate its dioxygenase activity, consume nitric oxide, and promote IDO protein nitration. Conclusion: IDO is a catalyst of physiological peroxidase reactions. Significance: IDO peroxidase activity has novel implications for the control and biological actions of this important immune regulatory enzyme.

show abstract

“…18,19 However, peroxidase enzymes are prone to inactivation from slow attack of hydrogen peroxide in the absence of other reductant substrates or when the ratio of H 2 O 2 /enzyme is large. 20,21 There are several irreversible damage pathways for heme proteins, including the oxidation of the heme ring and release of free iron, 22-26 the intramolecular cross-linking of amino acid residues, and dimerization or oligomerization of proteins resulting from intra-and inter-molecular radical reactions, 27-32 formation of amino acid peroxyl radicals, 29 Two strategies have been used to protect enzymes from damage by peroxide: (1) an impermeable barrier on the biosensor surface to prevent H 2 O 2 from diffusing into the films; 33 (2) a functional protection layer on the biosensor surface to react with H 2 O 2 to protect enzymes from damage. 34-36 The latter approach shows obvious advantages in selectivity and efficiency, since with the former method the barrier may also completely isolate the device from substrates.…”

Section: Introductionmentioning

confidence: 99%

Protecting Peroxidase Activity of Multilayer Enzyme-Polyion Films Using Outer Catalase Layers

Rusling

2007

J. Phys. Chem. B

View full text Add to dashboard Cite

Films constructed layer-by-layer on electrodes with architecture {protein/hyaluronic acid (HA)} n containing myoglobin (Mb) or horseradish peroxidase (HRP) were protected against protein damage by H 2 O 2 by using outer catalase layers. Peroxidase activity for substrate oxidation requires activation by H 2 O 2 , but {protein/HA} n films without outer catalase layers are damaged slowly and irreversibly by H 2 O 2 . The rate and extent of damage were decreased dramatically by adding outer catalase layers to decompose H 2 O 2 . Comparative studies suggest that protection results from catalase decomposing a fraction of the H 2 O 2 as it enters the film, rather than by an in-film diffusion barrier. The outer catalase layers controlled the rate of H 2 O 2 entry into inner regions of the film, and biased the system to favor electrocatalytic peroxide reduction over enzyme damage. Catalase-protected {protein/ HA} n films had an increased linear concentration range for H 2 O 2 detection. This approach offers an effective way to protect biosensors from damage by H 2 O 2 .

show abstract

Myoglobin-Induced Oxidative Damage: Evidence for Radical Transfer from Oxidized Myoglobin to Other Proteins and Antioxidants

Cited by 92 publications

References 45 publications

Reaction of Human Myoglobin and H2O2

Reaction of Human Myoglobin and H2O2

Human Indoleamine 2,3-Dioxygenase Is a Catalyst of Physiological Heme Peroxidase Reactions

Protecting Peroxidase Activity of Multilayer Enzyme-Polyion Films Using Outer Catalase Layers

Contact Info

Product

Resources

About