Reactions of Hypochlorous Acid with Tyrosine and Peptidyl-tyrosyl Residues Give Dichlorinated and Aldehydic Products in Addition to 3-Chlorotyrosine

Fu, Shanlin; Wang, Hongjie; Davies, Michael J.; Dean, Roger T.

doi:10.1074/jbc.275.15.10851

Cited by 95 publications

(68 citation statements)

References 63 publications

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“…50 Interestingly, the diClTyr to ClTyr ratio in lesion lipoproteins was high ( Table 4) compared to that found for reactions of HOCl with free and peptide-bound Tyr. 24 In contrast, analysis of SN-2 after removal of all lipoproteins showed comparatively fewer products and lower ratios of diClTyr to ClTyr (data not shown). A high ratio may be obtained under conditions of high local oxidant production (AJ Kettle, unpublished results), and our data supports the previous suggestion by Heinecke 52 that Tyr chlorination via myeloperoxidase activity is relatively specific for lesion lipoproteins.…”

Section: Discussionmentioning

confidence: 83%

“…21,22 Artifactual formation of m-Tyr, o-Tyr, DOPA, and diTyr during protein hydrolysis of atherosclerotic tissue using the methodology described herein has been investigated in detail. 21,23,24 The maximum artifactual formation of the analytes determined by this method consistently ranges from 20 mol/mol of m-Tyr, o-Tyr, and diTyr to 200 mol/mol of DOPA per parent amino acid.…”

Section: Hplc Analysesmentioning

confidence: 99%

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Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Upston

Niu

Brown

et al. 2002

The American Journal of Pathology

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126

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Oxidative modification of low-density lipoprotein is thought to promote arterial lipid accumulation and atherogenesis. Previous studies reported on the presence of certain lipid or protein oxidation products in lesions, although a systematic investigation measuring several oxidation parameters and the accumulation of nonoxidized lipids and antioxidants at various stages of atherosclerosis has not been performed in the same tissue. Using the intimal lipoprotein-containing fraction of human aortic lesions, we demonstrate here that cholesterol accumulated with lesion development and that this increase was already significant at the fatty streak stage. By comparison, cholesterylesters increased significantly only in fibrofatty and more complex lesions that also contained significantly increased amounts of cholesterylester hydro(pero)xides and 27-hydroxycholesterol. Cholesterylester hydroxides were the major lipid oxidation product detected. Despite accumulation of oxidized lipid, ␣-tocopherol was also present and maintained at a comparable level over the disease process. Of the oxidized protein moieties measured only o,o-dityrosine increased with disease, although chlorotyrosines were present at relatively high levels in all lesions compared to healthy vessels. Our data show that accumulation of nonoxidized lipid precedes that of oxidized lipid in human aortic lesions. The development of atherosclerosis to clinical manifestations is a protracted process that spans several decades. It is well established that lipids, specifically cholesterol, accumulate as the disease progresses 1 and that these lipids are derived from plasma low-density lipoprotein (LDL). Aberrant uptake of LDL and its associated lipids by intimal monocytes that have infiltrated from the blood is believed to generate foam cells and thereby initiate atherosclerosis. 2 Foam cells are the hallmark of the fatty streak/early lesion from which the more advanced and complicated lesions derive. In advanced lesions, a fibrous cap is formed from collagen and a lipid-rich necrotic core. Vessel lumen narrowing because of the enlarged fibrous cap and plaque rupture lead to clinical manifestations.The definitive mechanisms leading to the initiation and development of atherosclerosis are unknown. However, retention of LDL in the vessel wall because of interaction and complex formation with extracellular matrix components is well-documented 3 and is thought to be important. Further, a bulk of evidence suggests that oxidative modifications to LDL contribute to its retention. 4 -6 Both arterial wall retention and oxidative modification of LDL are thought to contribute to foam cell formation.In vitro studies with plasma LDL have shown that oxidative modifications proceed in different stages and involve changes to LDL's antioxidants, lipids, and protein components. The nature and extent of these alterations vary depending on the type of oxidant involved, the oxidant to lipoprotein ratio used, and the extent to which oxidation is allowed to proceed. Originally 4 the pa...

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Section: Discussionmentioning

confidence: 83%

Section: Hplc Analysesmentioning

confidence: 99%

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Upston

Niu

Brown

et al. 2002

The American Journal of Pathology

Self Cite

126

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“…In addition to these kinetic arguments, other processes such as hyperoxidation (19,20) and de-chlorination or metabolism (21,55) could have conceivably contributed to our inability to detect 3-Cl-Tyr in inflamed arteries. Examination of inflamed arterial tissue for dichlorinated species and 4-hydroxyphenylacetaldehydes (19,20) may be useful to assess a potential contribution of tyrosine hyperoxidation.…”

Section: Discussionmentioning

confidence: 91%

“…These include the low rate of reaction of tyrosine and peptidyl-tyrosyl residues with HOCl, with an estimated rate constant of ϳ40 M Ϫ1 s Ϫ1 (18). Also, 3-Cl-Tyr can be oxidized further to 3,5-dichlorotyrosine and mono-and dichlorinated 4-hydroxyphenylacetaldehydes (19,20). Furthermore, in biological systems, 3-Cl-Tyr is subject to metabolism and dechlorination (21).…”

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confidence: 99%

Assessment of Myeloperoxidase Activity by the Conversion of Hydroethidine to 2-Chloroethidium

Maghzal

Cergol

Shengule

et al. 2014

Journal of Biological Chemistry

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Background: Myeloperoxidase activity is commonly assessed in vivo by the accumulation of 3-chlorotyrosine. Results: Myeloperoxidase-derived chlorinating species specifically converted hydroethidine to 2-chloroethidium with efficiency superior to that of the corresponding conversion of tyrosine to 3-chlorotyrosine. Conclusion: Hydroethidine is useful to assess myeloperoxidase activity in vivo, in parallel with its simultaneous use to detect superoxide. Significance: 2-Chloroethidium is a useful additional marker of myeloperoxidase activity.

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“…This may be due to either the absence of free Tyr that might cross-link to proteinbound Tyr residues, or the steric constraints that may be imposed on the dimerization of Tyr-derived phenoxyl radicals formed on matrix proteins by the three-dimensional structure of the matrix. A previous study from this laboratory has revealed that di-Tyr can be generated on treatment of the globular protein BSA with HOCl [54], suggesting that that steric factors play an important role in determining the relative yield of di-Tyr in different situations.…”

Section: Discussionmentioning

confidence: 99%

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

Woods

Linton

Davies

2003

Biochemical Journal

107

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Oxidation is believed to play a role in atherosclerosis. Oxidized lipids, sterols and proteins have been detected in early, intermediate and advanced human lesions at elevated levels. The spectrum of oxidized side-chain products detected on proteins from homogenates of advanced human lesions has been interpreted in terms of the occurrence of two oxidative mechanisms, one involving oxygen-derived radicals catalysed by trace transition metal ions, and a second involving chlorinating species (HOCl or Cl2), generated by the haem enzyme myeloperoxidase (MPO). As MPO is released extracellularly by activated monocytes (and possibly macrophages) and is a highly basic protein, it would be expected to associate with polyanions such as the glycosaminoglycans of the extracellular matrix, and might result in damage being localized at such sites. In this study proteins extracted from extracellular matrix material obtained from advanced human atherosclerotic lesions are shown to contain elevated levels of oxidized amino acids [3,4-dihydroxyphenylalanine (DOPA), di-tyrosine, 2-hydroxyphenylalanine (o-Tyr)] when compared with healthy (human and pig) arterial tissue. These matrix-derived materials account for 83—96% of the total oxidized protein side-chain products detected in these plaques. Oxidation of matrix components extracted from healthy artery tissue, and model proteins, with reagent HOCl is shown to give rise to a similar pattern of products to those detected in advanced human lesions. The detection of elevated levels of DOPA and o-Tyr, which have been previously attributed to the occurrence of oxygen-radical-mediated reactions, by HOCl treatment, suggests an alternative route to the formation of these materials in plaques. This is believed to involve the formation and subsequent decomposition of protein chloramines.

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Reactions of Hypochlorous Acid with Tyrosine and Peptidyl-tyrosyl Residues Give Dichlorinated and Aldehydic Products in Addition to 3-Chlorotyrosine

Cited by 95 publications

References 63 publications

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Disease Stage-Dependent Accumulation of Lipid and Protein Oxidation Products in Human Atherosclerosis

Assessment of Myeloperoxidase Activity by the Conversion of Hydroethidine to 2-Chloroethidium

Detection of HOCl-mediated protein oxidation products in the extracellular matrix of human atherosclerotic plaques

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