Hypochlorous acid oxidizes methionine and tryptophan residues in myoglobin

Szuchman-Sapir, Andrea; Pattison, David I.; Ellis, Natasha A.; Hawkins, Clare L.; Davies, Michael J.; Witting, Paul K.

doi:10.1016/j.freeradbiomed.2008.06.010

Cited by 34 publications

(24 citation statements)

References 62 publications

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“…HOCl has previously been shown to oxidize key methionine residues in cytochrome c [16, 33] as well as methionines of actin [34], myoglobin [35] and cathepsin G [36]. To detect methionine sulfoxide residues in total α-crystallin, we used CNBr to specifically cleave methionines and visualized the cleavage products by SDS-PAGE and colloidal blue staining.…”

Section: Resultsmentioning

confidence: 99%

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

Brennan

Lee

Giblin

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Lens cataract is associated with protein oxidation and aggregation. Two proteins that cause cataract when deleted from the lens are methionine sulfoxide reductase A (MsrA) that repairs protein methionine sulfoxide (PMSO) oxidized proteins and α-crystallin which is a two subunit (αA and αB) chaperone. Here, we tested whether PMSO formation damages α-crystallin chaperone function and whether MsrA could repair PMSO-α-crystallin. Methods Total α-crystallin was oxidized to PMSO and evaluated by CNBr-cleavage and mass spectrometry. Chaperone activity was measured by light scattering using lysozyme as target. PMSO-α-crystallin was treated with MsrA, and repair was assessed by CNBr cleavage, mass spectrometry and recovery of chaperone function. The levels of α-crystallin-PMSO in the lenses of MsrA-knockout relative to wild-type mice were determined. Results PMSO oxidation of total α-crystallin (met 138 of αA and met 68 of αB) resulted in loss of α-crystallin chaperone activity. MsrA treatment of PMSO-α-crystallin repaired its chaperone activity through reduction of PMSO. Deletion of MsrA in mice resulted in increased levels of PMSO-α-crystallin. Conclusions Methionine oxidation damages α-crystallin chaperone function and MsrA can repair PMSO-α-crystallin restoring its chaperone function. MsrA is required for maintaining the reduced state of α-crystallin methionines in the lens. Significance Methionine oxidation of α-crystallin in combination with loss of MsrA repair causes loss of α-crystallin chaperone function. Since increased PMSO levels and loss of α-crystallin function are hallmarks of cataract, these results provide insight into the mechanisms of cataract development and likely those of other age-related diseases.

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Section: Resultsmentioning

confidence: 99%

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

Brennan

Lee

Giblin

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Owing to incapability of the cellular machinery for their reduction, the above-mentioned oxidation products modulate the function of the protein by changing the local protein structure, since they are not usually degraded by enzymes or the proteasome (Chang et al 2000) and can also accumulate and aggregate in the cells (Squier 2001). A number of state-of-the-art techniques, such as the reverse-phase high-performance liquid chromatography (RP-HPLC) combined with UV and fluorescence detection (Simat and Steinhart 1998;Simat et al 1994) or mass spectrometry (MS) ( Van de Weert et al 1998;Dominques et al 2003;Szuchman-Sapir et al 2008;Mouls et al 2009), are available for efficient analysis of tryptophan oxidation products. In fact, oxidized tryptophan residues, such as 5-HTP, Oia, NFK, and Kyn, have been reported to exhibit different fragmentation characteristics in both MALDIand ESI-tandem MS that in turn help in their identification by specific marker ions, in addition to their increment masses within a given ion series (Todorovski et al 2011).…”

Section: Overviewmentioning

confidence: 99%

Lipids and proteins—major targets of oxidative modifications in abiotic stressed plants

Anjum

Sofo

Scopa

et al. 2014

Environ Sci Pollut Res

283

160

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Stress factors provoke enhanced production of reactive oxygen species (ROS) in plants. ROS that escape antioxidant-mediated scavenging/detoxification react with biomolecules such as cellular lipids and proteins and cause irreversible damage to the structure of these molecules, initiate their oxidation, and subsequently inactivate key cellular functions. The lipid- and protein-oxidation products are considered as the significant oxidative stress biomarkers in stressed plants. Also, there exists an abundance of information on the abiotic stress-mediated elevations in the generation of ROS, and the modulation of lipid and protein oxidation in abiotic stressed plants. However, the available literature reflects a wide information gap on the mechanisms underlying lipid- and protein-oxidation processes, major techniques for the determination of lipid- and protein-oxidation products, and on critical cross-talks among these aspects. Based on recent reports, this article (a) introduces ROS and highlights their relationship with abiotic stress-caused consequences in crop plants, (b) examines critically the various physiological/biochemical aspects of oxidative damage to lipids (membrane lipids) and proteins in stressed crop plants, (c) summarizes the principles of current technologies used to evaluate the extent of lipid and protein oxidation, (d) synthesizes major outcomes of studies on lipid and protein oxidation in plants under abiotic stress, and finally, (e) considers a brief cross-talk on the ROS-accrued lipid and protein oxidation, pointing to the aspects unexplored so far.

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“…including amino acids, resulting in altered protein function and cellular injury ( 5,36 ). The MPO-dependent modifi cation of apoA-I structure and function have been studied previously.…”

Section: Downloaded Frommentioning

confidence: 99%

Preservation of biological function despite oxidative modification of the apolipoprotein A-I mimetic peptide 4F

White

Datta

Buck

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org Myeloperoxidase (MPO), an abundant heme protein released by activated leukocytes, catalyzes the oxidation of chloride ions by hydrogen peroxide (H 2 O 2 ) to yield hypochlorous acid (HOCl). MPO has been identifi ed as a biomarker for pathological conditions including sepsis, ischemic injury and atherosclerosis ( 1-4 ). Increased circulating levels of MPO are associated with increased coronary risk, and MPO colocalizes with macrophages in human atherosclerotic lesions ( 1, 2 ). HOCl is a potent oxidant whose cellular targets of action include thiols, amines, nucleotides, unsaturated fatty acids and lipoproteins ( 5 ). With respect to lipoprotein metabolism, HOCl impairs both LDL and HDL function. HOCl oxidizes apolipoprotein (apo) B100 and lipid components of LDL particles, resulting in increased scavenger receptor uptake of LDL by macrophages and the development of fatty lesions ( 6, 7 ). The HOCl-dependent oxidation of HDL converts it to a form that is proatherogenic (8)(9)(10)(11). Dysfunctional HDL particles demonstrate a reduced capacity to mediate ATPbinding cassette transporter A1 (ABCA1)-dependent cholesterol effl ux and are resistant to metabolism by hepatic enzyme systems ( 12-17 ). MPO and HOCl also inhibit the activity of the HDL-associated enzyme lecithin cholesterol acyl transferase (LCAT), thus attenuating the formation of mature ␣ -HDL particles ( 18 ). The MPO-catalyzed oxidation of HDL also attenuates anti-apoptotic and anti-infl ammatory effects of the lipoprotein ( 11 ). These changes are associated with reduced binding of HDL to scavenger receptor class B1 (SR-B1).Data suggest that the formation of dysfunctional HDL by MPO and HOCl is due principally to changes in the protein components of the particle (whereas higher concentrations may induce changes in the lipid composition

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Hypochlorous acid oxidizes methionine and tryptophan residues in myoglobin

Cited by 34 publications

References 62 publications

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

Methionine sulfoxide reductase A (MsrA) restores α-crystallin chaperone activity lost upon methionine oxidation

Lipids and proteins—major targets of oxidative modifications in abiotic stressed plants

Preservation of biological function despite oxidative modification of the apolipoprotein A-I mimetic peptide 4F

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