Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins

Ohshima, Hiroshi; Friesen, Marlin D.; Brouet, I.; Bartsch, Helmut

doi:10.1016/0278-6915(90)90173-k

Cited by 251 publications

(159 citation statements)

References 11 publications

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“…The link of urinary excretion of protein glycation, oxidation and nitration free adducts to flux of endogenous adduct formation is compromised where there is metabolism and repair of the free adducts. This applies to the repair of FL and MetSO free adducts by fructosamine 3-phosphokinase [27] and MetSO reductase [31], respectively, and metabolism of 3-NT to 3-nitro-4-hydroxyphenylacetic acid and 3-nitro-4-hydroxyphenyllactic acid [32]. Decreased renal tubular re-uptake and metabolism of glycation and oxidation free adducts in the diabetic state may give rise to increases in urinary excretion of free adducts disproportionate to the increase in de novo formation in tissue proteins.…”

Section: Discussionmentioning

confidence: 99%

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

et al. 2010

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Aims/hypothesis The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy. Methods Diabetes was induced in male Sprague-Dawley rats by 55 mg/kg streptozotocin and moderated by insulin (2 U twice daily). Diabetic and control rats were given thiamine or benfotiamine (7 or 70 mg kg −1 day −1 ) over 24 weeks. Plasma, urine and tissues were collected and analysed for protein damage by stable isotopic dilution analysis MS. Results There were two-to fourfold increases in fructosyllysine and AGE content of glomerular, retinal, sciatic nerve and plasma protein in diabetes. Increases in AGEs were reversed by thiamine and benfotiamine therapy but increases in fructosyl-lysine were not. Methionine sulfoxide content of plasma protein and 3-nitrotyrosine content of sciatic nerve protein were increased in diabetes. Plasma glycation free adducts were increased up to twofold in diabetes; the increases were reversed by thiamine. Urinary excretion of glycation, oxidation and nitration free adducts was increased by seven-to 27-fold in diabetes. These increases were reversed by thiamine and benfotiamine therapy. Conclusions/interpretation AGEs, particularly argininederived hydroimidazolones, accumulate at sites of microvascular complication development and have markedly increased urinary excretion rates in experimental diabetes. Thiamine and benfotiamine supplementation prevented tissue accumulation and increased urinary excretion of protein glycation, oxidation and nitration adducts. Similar effects may contribute to the reversal of early-stage clinical diabetic nephropathy by thiamine.

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Section: Discussionmentioning

confidence: 99%

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

et al. 2010

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“…NFK and 3-NT are also metabolised to kynurenine [49] and 3-nitro-4-hydroxyphenylacetic acid [50] respectively. The predicted high contribution of plasma protein and haemoglobin turnover to urinary excretion of hydroimidazolone free adducts may suggest there are enzymatic mechanisms to repair or metabolise these adducts too.…”

Section: Discussionmentioning

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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“…18 Peroxynitrite causes nitration of tyrosine residues on proteins to form nitrotyrosine. 29 This has been used as a marker of in vivo activity of peroxynitrite and, for example, is found in the intima of vessels with atherosclerotic lesions. 30 Myatt and coworkers have reported increased nitrotyrosine immunostaining, particularly in villous vascular endothelium, in preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia

Many

Hubel

Fisher

et al. 2000

The American Journal of Pathology

252

150

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In preeclampsia, poor placental perfusion may result in maternal endothelial dysfunction, but the pathways involved are largely unknown. Candidate placental mediators include products of oxidative stress released into the maternal circulation. Xanthine oxidase has been implicated in postischemic-reperfusion injury via the generation of superoxide anion radicals (superoxide; O 2 .؊ ) and hydrogen peroxide. We examined placentas and placental bed curettings and/or biopsies from preeclamptic control pregnant women to test the hypothesis that xanthine oxidase is a mediator of oxidative stress in placentas from women with preeclampsia. The expression of xanthine dehydrogenase/xanthine oxidase holoenzyme and the activity of xanthine oxidase, the isoform known to generate reactive oxygen species, were increased in a subpopulation of cytotrophoblasts of preeclamptic women. Additionally, the expression of superoxide dismutase, which would scavenge superoxide produced by xanthine oxidase, was reduced in the same cells. Preeclampsia, a pregnancy-specific disorder, is the leading cause of maternal mortality in the Western world and increases perinatal mortality fivefold. The clinical diagnosis is based on the new onset of hypertension and the appearance of proteinuria and edema during pregnancy. It is evident, however, that these findings are a small component of a multisystemic disease that reduces perfusion to virtually all of the organs in the body. 1 The hypothesis has been advanced that much of the disease could be explained by alterations in the function of vascular endothelium. Increasing data support this hypothesis. 2 The more complete hypothesis posits that the placenta, likely in response to reduced perfusion, produces a circulating factor(s) that alters endothelial cell function. 2 Among the candidate molecules are products resulting from oxidative stress. 3 Oxidative stress, the result of freeradical generation in excess of protective mechanisms, is suggested as an important component of other disorders that affect endothelial function, including diabetes and atherosclerosis. 4,5 Evidence for oxidative stress in preeclampsia includes elevated lipid hydroperoxides or their metabolites and reduced plasma antioxidant activity. 3,6 -8 Xanthine oxidase, which metabolizes xanthine and hypoxanthine to uric acid with production of superoxide and hydrogen peroxide, is an integral mediator of reactive oxygen species generation in many settings. Usually, this enzyme is present as the holoenzyme xanthine dehydrogenase/xanthine oxidase (XDH/XO). The dehydrogenase isoform (XDH) converts purines to uric acid with reducton of nicotinamide-adenine dinucleotide (NAD) to reduced NAD (NADH). With hypoxia and in response to several cytokines, XDH/XO synthesis increases, and the conversion of the enzyme to the XO form is enhanced. 9 Reduced organ perfusion and subsequent reperfusion are proposed to result in increased XO during reduced flow and in subsequent formation of reactive oxygen species with reperfusion. The inadequate pla...

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Nitrotyrosine as a new marker for endogenous nitrosation and nitration of proteins

Cited by 251 publications

References 11 publications

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

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

Invasive Cytotrophoblasts Manifest Evidence of Oxidative Stress in Preeclampsia

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