Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.

Wells-Knecht, Mary C.; Lyons, Timothy J.; McCance, David R.; Thorpe, Suzanne R.; Baynes, John W.

doi:10.1172/jci119599

Cited by 137 publications

(72 citation statements)

References 47 publications

(33 reference statements)

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“…These data are consistent with earlier work from our laboratory in which we reported a strong correlation between levels of MetSO and CML in human skin collagen, both in vivo and in glycoxidation reactions in vitro. In these studies of both collagen from biopsies and collagen glycoxidized in vitro, we observed an approximately 100-fold higher concentration of MetSO, compared to CML (9). In recent work, Thornalley et al [5] also reported that the level of MetSO in plasma proteins was over 30-fold higher than that of CML.…”

Section: Relative Rates Of Glycoxidative and Lipoxidative Damagesupporting

confidence: 52%

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Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A

Brock¹,

Ames²,

Thorpe³

et al. 2007

Archives of Biochemistry and Biophysics

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Chemical modification of proteins by reactive oxygen species affects protein structure, function and turnover during aging and chronic disease. Some of this damage is direct, for example by oxidation of amino acids in protein by peroxide or other reactive oxygen species, but autoxidation of ambient carbohydrates and lipids amplifies both the oxidative and chemical damage to protein and leads to formation of advanced glycoxidation and lipoxidation end-products (AGE/ALEs). In previous work we have observed the oxidation of methionine during glycoxidation and lipoxidation reactions, and in the present work we set out to determine if methionine sulfoxide (MetSO) in protein was a more sensitive indicator of glycoxidative and lipoxidative damage than AGE/ALEs. We also investigated the sites of methionine oxidation in a model protein, ribonuclease A (RNase), in order to determine whether analysis of the site specificity of methionine oxidation in proteins could be used to indicate the source of the oxidative damage, i.e. carbohydrate or lipid. We describe here the development of an LC/MS/MS for quantification of methionine oxidation at specific sites in RNase during glycoxidation or lipoxidation by glucose or arachidonate, respectively. Glycoxidized and lipoxidized RNase were analyzed by tryptic digestion, followed by reversed phase HPLC and mass spectrometric analysis to quantify methionine and methionine sulfoxide containing peptides. We observed that: 1) compared to AGE/ALEs, methionine sulfoxide was a more sensitive biomarker of glycoxidative or lipoxidative damage to proteins; 2) regardless of oxidizable substrate, the relative rate of oxidation of methionine residues in RNase was Met 29 > Met 30 > Met 13 , with Met 79 being resistant to oxidation; and 3) arachidonate produced a significantly greater yield of MetSO, compared to glucose. The methods developed here should be useful for assessing a protein's overall exposure to oxidative stress from a variety of sources in vivo.

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Section: Relative Rates Of Glycoxidative and Lipoxidative Damagesupporting

confidence: 52%

“…Quantification of MetSO by amino acid analysis was performed as described previously [9], based on the procedure of Shechter et al [10]. Briefly, Met residues were converted to homoserine lactone by reaction with cyanogen bromide (CNBr); this procedure was repeated three times to achieve complete oxidation of Met.…”

Section: Amino Acid Analysismentioning

confidence: 99%

Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A

Brock¹,

Ames²,

Thorpe³

et al. 2007

Archives of Biochemistry and Biophysics

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“…As proposed by Dunn et al [2], this indicates that skin collagen undergoes relatively more initial glycation than lens protein, but is exposed to less oxidative stress. The last finding is corroborated by the much lower levels in skin collagen compared with lens protein of o-tyrosine, a marker of oxidative damage to tissue proteins [42,43]. In cartilage collagen, as in skin collagen, lower levels of CML and CEL are present than of FL, suggesting that in cartilage oxidative processes may also play a less important role than in the lens.…”

Section: Maillard Reaction Products In Cartilage Compared With Skin Amentioning

confidence: 91%

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Verzijl

DeGroot

Oldehinkel³

et al. 2000

Biochemical Journal

235

100

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Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated with a stiffer collagen network in cartilage. However, even in cartilage, pentosidine levels themselves represent 1 cross-link per 20 collagen molecules, and as such cannot be expected to contribute substantially to the increase in collagen network stiffness. In the present study, we investigated a broad range of Maillard reaction products in cartilage collagen in order to determine whether pentosidine serves as an adequate marker for AGE levels. Not only did the well-characterized AGEs pentosidine, N ε -(carboxymethyl)lysine, and N ε -(carboxyethyl)lysine increase with age in cartilage collagen (all P 0.0001), but also general measures of AGE cross-linking, such as browning and fluorescence (both P 0.0001), increased. The levels of these AGEs are all higher in cartilage collagen than in skin collagen. INTRODUCTIONDuring aging, long-lived proteins such as collagen and eye lens proteins are non-enzymically modified by reducing sugars. The major initial product is fructose-lysine (FL) [1,2], which results from glycation of ε-amino groups on lysine residues. In subsequent Maillard or browning reactions, products known as advanced glycation end products (AGEs) are formed from FL [3,4], and accumulate with age in long-lived proteins [1,2,[5][6][7][8]. These AGEs include structurally characterized adducts, such as N ε -(carboxymethyl)lysine (CML) [1][2][3] and N ε -(carboxyethyl)-lysine (CEL) [9], fluorescent cross-links, such as pentosidine formed between lysine and arginine residues [5,10], as well as chemically unidentified compounds which result in proteinbound browning or fluorescence, and cross-linking [11][12][13][14].In comparison with other collagen-rich tissues such as skin, cartilage contains relatively large amounts of pentosidine [5,15]. Pentosidine levels in articular cartilage increase linearly with age [6-8], as was previously described for skin collagen [16] and lens proteins [10]. Pentosidine is also present in the proteoglycans in articular cartilage [17], but appears to be localized predominantly in the collagen component of the tissue [7]. Age-related accumulation of AGE cross-links in articular cartilage collagen may result in increased stiffening of the collagen network, as was shown after in itro ribosylation of cartilage [7]. Thus AGE cross-linking in i o may contribute to the age-related impairment of the ability of articular collagen to resist mechanically induced damage and eventually cartilage degeneration [18][19][20].Abbreviations used : AGE, advanced glycation end product ; CEL, N ε -(carboxyethyl)lysine ; CML, N ε -(carboxymethyl)lysine ; FL, fructose-lysine. 1 To whom correspondence should be addressed (e-mail JM.TeKoppele!pg.tno.nl).As a functional measure of glycation the digestibility o...

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“…Other important and widely studied AGEs are N " -carboxymethyl-lysine (CML), N " -carboxyethyl-lysine (CEL) and pentosidine [5]. Major quantitative markers of oxidative damage to proteins are methionine sulphoxide (MetSO) and N-formylkynurenine (NFK), formed by the oxidation of methionine and tryptophan respectively [7,8], and a widely studied marker of nitration damage to proteins is 3-nitrotyrosine (3-NT) [9] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes

et al. 2005

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Aims/hypothesis: Hyperglycaemia in diabetes is associated with increased glycation, oxidative stress and nitrosative stress. Proteins modified consequently contain glycation, oxidation and nitration adduct residues, and undergo cellular proteolysis with release of corresponding free adducts. These free adducts leak into blood plasma for eventual renal excretion. The aim of this study was to perform a comprehensive quantitative analysis of protein glycation, oxidation and nitration adduct residues in plasma protein and haemoglobin as well as of free adducts in plasma and urine to quantify increased protein damage and flux of proteolytic degradation products in diabetes. Methods: Type 1 diabetic patients (n=21) and normal healthy control subjects (n=12) were studied. Venous blood samples, with heparin anticoagulant, and 24-h urine samples were taken. Samples were analysed for protein glycation, oxidation and nitration adducts by a quantitative comprehensive screening method using liquid chromatography with triple quadrupole mass spectrometric detection. Results: In type 1 diabetic patients, the concentrations of protein glycation, oxidation and nitration adduct residues increased up to three-fold in plasma protein and up to one-fold in haemoglobin, except for decreases in pentosidine and 3-nitrotyrosine residues in haemoglobin when compared with normal control subjects. In contrast, the concentrations of protein glycation and oxidation free adducts increased up to ten-fold in blood plasma, and urinary excretion increased up to 15-fold in diabetic patients. Conclusions/interpretation: We conclude that there are profound increases in proteolytic products of glycated and oxidised proteins in diabetic patients, concurrent with much lower increases in protein glycation and oxidation adduct residues.

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Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.

Cited by 137 publications

References 47 publications

Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A

Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A

Age-related accumulation of Maillard reaction products in human articular cartilage collagen

Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes

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