The Experts below are selected from a list of 11502 Experts worldwide ranked by ideXlab platform
Dimitrios Tsikas - One of the best experts on this subject based on the ideXlab platform.
-
What we-authors, reviewers and editors of scientific work-can learn from the analytical history of biological 3-Nitrotyrosine.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2017Co-Authors: Dimitrios TsikasAbstract:Tyrosine and tyrosine residues in proteins are attacked by the reactive oxygen and nitrogen species peroxynitrite (O=N-OO-) to generate 3-Nitrotyrosine (3-NT) and 3-Nitrotyrosine-proteins (3-NTProt), respectively. 3-NT and 3-NTProt are widely accepted as biomarkers of nitr(os)ative stress. Over the years many different analytical methods have been reported for 3-NT and 3-NTProt. Reported concentrations often differ by more than three orders of magnitude, indicative of serious analytical problems. Strategies to overcome pre-analytical and analytical shortcomings and pitfalls have been proposed. The present review investigated whether recently published work on the quantitative measurement of biological 3-Nitrotyrosine did adequately consider the analytical past of this biomolecule. 3-Nitrotyrosine was taken as a representative of biomolecules that occur in biological samples in the pM-to-nM concentration range. This examination revealed that in many cases the main protagonists involved in the publication of scientific work, i.e., authors, reviewers and editors, failed to do so. Learning from the analytical history of 3-Nitrotyrosine means advancing analytical and biological science and implies the following key issues. (1) Choosing the most reliable analytical approach in terms of sensitivity and accuracy; presently this is best feasible by stable-isotope dilution tandem mass spectrometry coupled with gas chromatography (GC-MS/MS) or liquid chromatography (LC-MS/MS). (2) Minimizing artificial formation of 3-Nitrotyrosine during sample work up, a major pitfall in 3-Nitrotyrosine analysis. (3) Validating adequately the final method in the intendent biological matrix and the established concentration range. (4) Inviting experts in the field for critical evaluation of the novelty and reliability of the proposed analytical method, placing special emphasis on the compliance of the analytical outcome with 3-Nitrotyrosine concentrations obtained by validated GC-MS/MS and LC-MS/MS methods.
-
Homoarginine and 3-Nitrotyrosine in patients with takotsubo cardiomyopathy
International journal of cardiology, 2014Co-Authors: Arslan Arinc Kayacelebi, Thanh H. Nguyen, Christopher Neil, John D. Horowitz, Jens Jordan, Dimitrios TsikasAbstract:In recent years, homoargininewas shown to be a cardiovascular risk factor [1], and to herald a poor prognosis in heart failure patients [2]. Yet, the underlying mechanism is elusive. Human and animal studies suggest that the enzyme responsible for the biosynthesis of homoarginine is arginine:glycine amidinotransferase (AGAT) [3–5]. Previously, excessive myocardial AGATgene expressionwas observed in heart failure; the authors implicated AGAT in cardiac creatine synthesis [6]. This finding suggests that homoarginine synthesis in the myocardiummay be elevated in heart failure. Thus far, there is no information about the homoarginine homeostasis in takotsubo cardiomyopathy (TTC) and which potential role this quite neglected non-proteinogenic amino acid may play in the development and recovery of TTC. In TTC patients we recently observed that the plasma concentration of asymmetric dimethylarginine (ADMA), another arginine homologue, is lower than the control, whereas the responsiveness to nitric oxide (NO) is substantially greater compared to healthy females [7]. This is of particular interest, because both L-arginine and L-homoarginine serve as substrates for NO synthases (NOS), while ADMA inhibits NOScatalyzed production of NO from these substrates [8]. The aim of the present study was to measure plasma homoarginine concentration inTTC patients and healthy controls of a previous study [7] and to determine its relationship to 3-Nitrotyrosine, a biomarker of NO-related oxidative stress. Plasma homoarginine and 3Nitrotyrosine were measured by validated, previously reported gas chromatography-tandem mass spectrometry (GC-MS/MS) methodologies [9,10]. Written informed consent was provided by all subjects included in the study, and the study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the local Ethics Committee of the Central Northern Adelaide Health Service: the Queen Elizabeth Hospital and Lyell McEwin Hospital (protocol number, 009014). The plasma concentration of homoarginine was significantly reduced in TTC patients compared to healthy controls (mean ± SEM; 1298 ± 112 nmol/L vs. 2094 ± 321 nmol/L; median 1403 nmol/L vs. 1634 nmol/L) (Fig. 1A). 3-Nitrotyrosine plasma concentrations were similar in TTC patients and in healthy controls (mean ± SEM; 2355 ± 217 pmol/L vs. 2227 ± 146 pmol/L; median 1915 pmol/L vs. 2170 pmol/L) (Fig. 1B). Pearson correlation between homoarginine and 3-Nitrotyrosine concentrations revealed a significant negative relationship in TTC patients (Fig. 2A). In contrast, a positive relationship was observed in the control group (Fig. 2B). No relationship was obtained when all homoarginine and 3-Nitrotyrosine data from TTC patients and controls were correlated (not shown). In the TTC patients, plasma homoarginine concentration correlated inversely with systolic blood pressure (SBP) (Fig. 2C). It is worth mentioning that plasma homoarginine concentrationwas found to correlate positively with SBP in an elderly population (50–87 years) non-suffering from takotsubo cardiomyopathy [11]. In contrast, plasma 3-Nitrotyrosine concentration did not correlate with SBP (Fig. 2C). Our study indicates that plasma homoarginine concentrations are reduced in TTC patients. They are considerably lower than those measured by us and others in healthy subjects [1–5]. With the exception of four TTC patients, the plasma concentrations of 3Nitrotyrosine measured in the other TTC patients and in the control subjects are comparable with those reported in the literature for healthy and ill subjects. The limited number of TTC patients and healthy controls investigated in our study limits the power of our findings. Nevertheless, the results of the present study in TTC supports recent studies indicating homoarginine as a novel marker of cardiovascular disease [1–5]. In contrast to elderly males and females with normal or impaired glucose metabolism or with type 2 diabetes mellitus but without TTC [11], in our TTC patients there was a negative correlation
-
Mass spectrometry and 3-Nitrotyrosine: strategies, controversies, and our current perspective.
Mass spectrometry reviews, 2013Co-Authors: Dimitrios Tsikas, Mark W. DuncanAbstract:Reactive-nitrogen species (RNS) such as peroxynitrite (ONOO(-)), that is, the reaction product of nitric oxide ((•)NO) and superoxide (O2(-•)), nitryl chloride (NO2Cl) and (•)NO2 react with the activated aromatic ring of tyrosine to form 3-Nitrotyrosine. This modification, which has been known for more than a century, occurs to both the free form of the amino acid (i.e., soluble/free tyrosine) and to tyrosine residues covalently bound within the backbone of peptides and proteins. Nitration of tyrosine is thought to be of biological significance and has been linked to health and disease, but determining its role has proved challenging. Several key questions have been the focus of much of the research activity: (a) to what extent is free/soluble tyrosine nitrated in biological tissues and fluids, and (b) are there specific site(s) of nitration within peptides/proteins and to what extent (i.e., stoichiometry) does this modification occur? These issues have been addressed in a wide range of sample types (e.g., blood, urine, CSF, exhaled breath condensate and various tissues) and a diverse array of physiological/pathophysiological scenarios. The accurate determination of nitrated tyrosine is, however, a stumbling block. Despite extensive study, the extent to which nitration occurs in vivo, the specificity of the nitration reaction, and its importance in health and disease, remain unclear. In this review, we highlight the analytical challenges and discuss the approaches adopted to address them. Mass spectrometry, in combination with either gas chromatography (GC-MS, GC-MS/MS) or liquid chromatography (LC-MS/MS), has played the central role in the analysis of 3-Nitrotyrosine and tyrosine-nitrated biological macromolecules. We discuss its unique attributes and highlight the role of stable-isotope labeled 3-Nitrotyrosine analogs in both accurate quantification, and in helping to define the biological relevance of tyrosine nitration. We show that the application of sophisticated mass spectrometric techniques is advantageous if not essential, but that this alone is by no means a guarantee of accurate findings. We discuss the important analytical challenges in quantifying 3-Nitrotyrosine, possible workarounds, and we attempt to make sense of the disparate findings that have been reported so far.
-
Analytical methods for 3-Nitrotyrosine quantification in biological samples: the unique role of tandem mass spectrometry
Amino Acids, 2012Co-Authors: Dimitrios TsikasAbstract:Reactive-nitrogen species, such as peroxynitrite (ONOO^−) and nitryl chloride (NO_2Cl), react with the aromatic ring of tyrosine in soluble amino acids and in proteins to form 3-Nitrotyrosine. The extent of nitration can be quantified by measuring 3-Nitrotyrosine in biological matrices, such as blood, urine, and tissue. This article reviews and discusses current analytical methodologies for the quantitative determination of 3-Nitrotyrosine in their soluble and protein-associated forms, with the special focus being on free 3-Nitrotyrosine. Special emphasis is given to analytical approaches based on the tandem mass spectrometry methodology. Pitfalls and solutions to overcome current methodological problems are emphasized and requirements for quantitative analytical approaches are recommended. The reliability of current analytical methods and the suitability of 3-Nitrotyrosine as a biomarker of nitrative stress are thoroughly examined.
-
Determination of 3-Nitrotyrosine in human urine at the basal state by gas chromatography-tandem mass spectrometry and evaluation of the excretion after oral intake.
Journal of chromatography. B Analytical technologies in the biomedical and life sciences, 2005Co-Authors: Dimitrios Tsikas, Anja Mitschke, Maria-theresia Suchy, Frank-mathias Gutzki, Dirk O. StichtenothAbstract:Abstract 3-Nitrotyrosine (NO2Tyr) is a potential biomarker of reactive-nitrogen species (RNS) including peroxynitrite. 3-Nitrotyrosine occurs in human plasma in its free and protein-associated forms and is excreted in the urine. Measurement of 3-Nitrotyrosine in human plasma is invasive and associated with numerous methodological problems. Recently, we have described an accurate method based on gas chromatography (GC)–tandem mass spectrometry (MS) for circulating 3-Nitrotyrosine. The present article describes the extension of this method to urinary 3-Nitrotyrosine. The method involves separation of urinary 3-Nitrotyrosine from nitrite, nitrate and l -tyrosine by HPLC, preparation of the n-propyl-pentafluoropropionyltrimethylsilyl ether derivatives of endogenous 3-Nitrotyrosine and the internal standard 3-nitro- l -[2H3]tyrosine, and GC–tandem MS quantification in the selected-reaction monitoring mode under negative-ion chemical ionization conditions. In urine of ten apparently healthy volunteers (years of age, 36.5 ± 7.2) 3-Nitrotyrosine levels were determined to be 8.4 ± 10.4 nM (range, 1.6–33.2 nM) or 0.46 ± 0.49 nmol/mmol creatinine (range, 0.05–1.30 nmol/mmol creatinine). The present GC–tandem MS method provides accurate values of 3-Nitrotyrosine in human urine at the basal state. After oral intake of 3-nitro- l -tyrosine by a healthy volunteer (27.6 μg/kg body weight) 3-nitro- l -tyrosine appeared rapidly in the urine and was excreted following a biphasic pharmacokinetic profile. Approximately one third of administered 3-nitro- l -tyrosine was excreted within the first 8 h. The suitability of the non-invasive measurement of urinary 3-Nitrotyrosine as a method of assessment of oxidative stress in humans remains to be established.
R. J. Ferrante - One of the best experts on this subject based on the ideXlab platform.
-
increased 3 Nitrotyrosine and oxidative damage in mice with a human copper zinc superoxide dismutase mutation
Annals of Neurology, 1997Co-Authors: R. J. Ferrante, Russell T. Matthews, Neil W. Kowall, Leslie A. Shinobu, Jörg B. Schulz, Craig E. Thomas, Mark E. Gurney, Flint M BealAbstract:Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of-function may be an enhanced ability of the mutant SOD1 to generate .OH radicals or to facilitate peroxynitrite-mediated nitration of proteins. We found significant increases in concentrations of 3-Nitrotyrosine, a marker of peroxynitrite-mediated nitration, in upper and lower spinal cord and in cerebral cortex of transgenic mice with the FALS-associated G93A mutation. Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration.
-
Increased 3-Nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis.
Annals of neurology, 1997Co-Authors: M. F. Beal, R. J. Ferrante, Susan E. Browne, Russell T. Matthews, Neil W. Kowall, Robert H. BrownAbstract:The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-Nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-Nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-Nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.
-
Increased 3-Nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation
Annals of neurology, 1997Co-Authors: R. J. Ferrante, Russell T. Matthews, Neil W. Kowall, Leslie A. Shinobu, Jörg B. Schulz, Craig E. Thomas, Mark E. Gurney, M. Flint BealAbstract:Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of-function may be an enhanced ability of the mutant SOD1 to generate .OH radicals or to facilitate peroxynitrite-mediated nitration of proteins. We found significant increases in concentrations of 3-Nitrotyrosine, a marker of peroxynitrite-mediated nitration, in upper and lower spinal cord and in cerebral cortex of transgenic mice with the FALS-associated G93A mutation. Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration.
Chiaki Isobe - One of the best experts on this subject based on the ideXlab platform.
-
Remarkable increase in 3-Nitrotyrosine in the cerebrospinal fluid in patients with lacunar stroke.
Brain research, 2009Co-Authors: Chiaki Isobe, Takashi Abe, Yasuo TerayamaAbstract:The goal of our study was whether free radicals contribute to the pathogenesis of the lacunar stroke to investigate the day after hospitalization, the concentrations of 3-Nitrotyrosine and tyrosine in the cerebrospinal fluid (CSF) from living patients. The subjects included 20 living patients with lacunar stroke and 20 controls. The NIH stroke scale score was used to assess the severity of the stroke, including that the patients were mild cases. There was no expansion of the infarct lesion in the brain, as assessed by CT on the day following admission. The concentration of 3-Nitrotyrosine was significantly higher in patients with lacunar stroke. In contrast, the concentration of tyrosine did not differ between the two groups. Furthermore, the 3-Nitrotyrosine/tyrosine ratio was significantly higher in patients with lacunar stroke than in controls. Our results show that free radicals are produced in the CSF of lacunar stroke patients and that nitration of neuronal proteines is enhanced under this condition. These obsetvations suggest that lacunar stroke patients should be treated with edaravon, which is a free radical scavenger usually prescribed for cases of major strokes, as it will likely improve the prognosis of these patients.
-
Alterations of 3-Nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease
Neuroscience letters, 1999Co-Authors: Hideo Tohgi, Takashi Abe, Kinya Yamazaki, Takahiko Murata, Eri Ishizaki, Chiaki IsobeAbstract:To investigate the significance of nitric oxide (NO) -mediated neuron death in aging and Alzheimer's disease (AD), the 3-Nitrotyrosine concentration in the cerebrospinal fluid (CSF) was investigated in neurologically normal controls and patients with AD. The 3-Nitrotyrosine concentration and the 3-Nitrotyrosine/tyrosine ratio significantly increased with advancing age, whereas the tyrosine concentration was unaltered. In patients with AD, the 3-Nitrotyrosine concentration and the 3-Nitrotyrosine/tyrosine ratio increased significantly (>six-fold) compared with controls of similar age, and increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change. These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and/or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD.
-
Remarkable increase in cerebrospinal fluid 3-Nitrotyrosine in patients with sporadic amyotrophic lateral sclerosis
Annals of neurology, 1999Co-Authors: Hideo Tohgi, Takashi Abe, Kinya Yamazaki, Takahiko Murata, Eri Ishizaki, Chiaki IsobeAbstract:To investigate the significance of peroxynitrite-mediated oxidative damage in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS), the concentrations of 3-Nitrotyrosine and tyrosine in the cerebrospinal fluid (CSF) of patients with SALS were determined. The concentration of 3-Nitrotyrosine and the 3-Nitrotyrosine/ tyrosine ratio in patients with SALS were approximately seven times those of controls. Thus, the present findings in living patients provide in vivo evidence for a possible role of peroxynitrite, a mediator of oxidative stress, and increased nitration of tyrosine residues in the pathogenesis of SALS.
Nurten Türközkan - One of the best experts on this subject based on the ideXlab platform.
-
Effects of taurine on nitric oxide and 3-Nitrotyrosine levels in spleen during endotoxemia.
Neurochemical research, 2011Co-Authors: Filiz Sezen Bircan, Nurten Türközkan, Barboros Balabanli, Gonca OzanAbstract:Taurine (2-aminoethanesulfonic acid) is a free sulfur-containing β-amino acid which has antioxidant, antiinflammatory and detoxificant properties. In the present study, the role of endotoxemia on peroxynitrite formation via 3-Nitrotyrosine (3-NT) detection, and the possible antioxidant effect of taurine in lipopolysaccharide (LPS)-treated guinea pigs were aimed. 40 adult male guinea pigs were divided into four groups; control, endotoxemia, taurine and taurine+endotoxemia. Animals were administered taurine (300 mg/kg), LPS (4 mg/kg) or taurine plus LPS intraperitoneally. After 6 h of incubation, when highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and spleen samples were collected. The amounts of 3-Nitrotyrosine and taurine were measured by HPLC, and reactive nitrogen oxide species (NOx) which are stable end products of nitric oxide was measured spectrophotometrically in spleen tissues. LPS administration significantly decreased the concentration of taurine whilst increased levels of 3-NT and NOx compared with control group. It was determined that taurine treatment decreased the levels of 3-Nitrotyrosine and NOx in taurine+endotoxemia group. The group in which taurine was administered alone, contradiction to well-known antioxidant effect, taurine caused elevated concentration of 3-NT and NOx. This data suggest that taurine protects spleen against oxidative damage in endotoxemic conditions. However, the effect of taurine is different when it is administered alone. In conclusion, taurine may act as an antioxidant during endotoxemia, and as a prooxidant in healthy subjects at this dose.
-
Effect of Taurine on Liver Xanthine Oxidase Activity and 3-Nitrotyrosine Level in Endotoxemia
Gazi Medical Journal, 2011Co-Authors: Nurten Türközkan, Gonca Ozan, Filiz Sezen Bircan, Nihal SahinAbstract:Objective: Taurine, a semi-essential and sulphur-containing β-amino acid, is not incorporated into proteins. It has been shown in many in vitro and in vivo studies to have cytoprotective effects, and these actions are often attributed to an antioxidant mechanism. The purpose of this study was to investigate the effect of taurine on 3-Nitrotyrosine production and xanthine oxidase activity in hepatocytes during endotoxemia. Methods: In this study, 40 adult male Dunkin Hartley guinea pig were randomly divided into four groups: control, taurine, endotoxemia and taurine plus endotoxemia (n=10). Animals were administered taurine (300 mg/kg, a single dose), lipopolysaccharide (4 mg/kg), or taurine plus lipopolysaccharide intraperitoneally. After six hours of incubation, when the highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and liver samples were collected. The amount of 3-Nitrotyrosine was measured by HPLC and xanthine oxidase enzyme activity was measured spectrophotometrically. Results: Lipopolysaccharide administration significantly increased protein 3-Nitrotyrosine levels and xanthine oxidase activity in hepatic tissue compared with the control group (p
-
Effect of Taurine on Liver Xanthine Oxidase Activity and 3-Nitrotyrosine Level in Endotoxemia Endotoksemide Taurinin Karaciğer Ksantin Oksidaz Aktivitesi ve 3-Nitrotirozin Düzeylerine Etkisi
2011Co-Authors: Nurten Türközkan, Gonca Ozan, Filiz Sezen BircanAbstract:SUMMARY Objective: Taurine, a semi-essential and sulphur-containing β-amino acid, is not incorporated into proteins. It has been shown in many in vitro and in vivo studies to have cytoprotective effects, and these actions are often attributed to an antioxidant mechanism. The purpose of this study was to investigate the effect of taurine on 3-Nitrotyrosine production and xanthine oxidase activity in hepatocytes during endotoxemia. Methods: In this study, 40 adult male Dunkin Hartley guinea pig were randomly divided into four groups: control, taurine, endotoxemia and taurine plus endotoxemia (n=10). Animals were administered taurine (300 mg/kg, a single dose), lipopolysaccharide (4 mg/kg), or taurine plus lipopolysaccharide intraperitoneally. After six hours of incubation, when the highest blood levels of taurine and endotoxin were attained, the animals were sacrificed and liver samples were collected. The amount of 3-Nitrotyrosine was measured by HPLC and xanthine oxidase enzyme activity was measured spectrophotometrically. Results: Lipopolysaccharide administration significantly increased protein 3-Nitrotyrosine levels and xanthine oxidase activity in hepatic tissue compared with the control group (p
-
The relationship between taurine and 3-Nitrotyrosine level of hepatocytes in experimental endotoxemia.
Neurochemical research, 2007Co-Authors: Hüsamettin Erdamar, Nurten Türközkan, Barboros Balabanli, Gonca Ozan, Filiz Sezen BircanAbstract:It has been proposed that taurine may function as an oxidant in a dose-dependent manner in vivo and in vitro. The present study was carried out to investigate the relationship between taurine concentration and 3-Nitrotyrosine level, a stable marker of peroxynitrite action, in hepatocytes of guinea pig in endotoxemia before and after taurine administration. The levels of taurine and 3-Nitrotyrosine were measured by HPLC method. In the present study, taurine was low concentration in hepatocytes exposed to endotoxemia. In taurine plus endotoxin treated animals, HPLC analysis showed higher taurine level compared with animals only supplemented with taurine. But 3-Nitrotyrosine levels were same in both taurine alone and taurine plus endotoxin groups. In conclusion, taurine is able to prevent the damaging effect of peroxynitrite, at concentration measured in hepatocytes, in our experimental conditions.
-
Effects of melatonin on 3-Nitrotyrosine formation and energy charge ratio in guinea pig kidney in LPS-induced stress.
Cell biochemistry and function, 2005Co-Authors: Behzat Çimen, Nurten Türközkan, Ali Ünlü, M. Kemal ErbilAbstract:The aim of this study was to evaluate the effects of Escherichia coli-derived lipopolysaccharide on guinea pig kidney by measuring the energy charge ratio and 3-Nitrotyrosine levels. In addition the possible protective role of melatonin against lipopolysaccharide-mediated peroxynitrite formation and energy depletion of kidney was determined. Guinea pigs were either pretreated with melatonin or saline (for the control) followed by intraperitoneal administration of E. coli. Six hours after the administration of E. coli, guinea pig kidney ATP, ADP, AMP and 3-Nitrotyrosine levels were measured by reverse-phase high performance liquid chromatography. There was a significant increase in the formation of 3-Nitrotyrosine and decrease in energy charge in the endotoxin-induced group. However melatonin administration prevented 3-Nitrotyrosine formation while failing to prevent or restore changes in the energy charge ratio of the kidney.
Russell T. Matthews - One of the best experts on this subject based on the ideXlab platform.
-
increased 3 Nitrotyrosine and oxidative damage in mice with a human copper zinc superoxide dismutase mutation
Annals of Neurology, 1997Co-Authors: R. J. Ferrante, Russell T. Matthews, Neil W. Kowall, Leslie A. Shinobu, Jörg B. Schulz, Craig E. Thomas, Mark E. Gurney, Flint M BealAbstract:Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of-function may be an enhanced ability of the mutant SOD1 to generate .OH radicals or to facilitate peroxynitrite-mediated nitration of proteins. We found significant increases in concentrations of 3-Nitrotyrosine, a marker of peroxynitrite-mediated nitration, in upper and lower spinal cord and in cerebral cortex of transgenic mice with the FALS-associated G93A mutation. Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration.
-
Increased 3-Nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis.
Annals of neurology, 1997Co-Authors: M. F. Beal, R. J. Ferrante, Susan E. Browne, Russell T. Matthews, Neil W. Kowall, Robert H. BrownAbstract:The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-Nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-Nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-Nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.
-
Increased 3-Nitrotyrosine and oxidative damage in mice with a human copper/zinc superoxide dismutase mutation
Annals of neurology, 1997Co-Authors: R. J. Ferrante, Russell T. Matthews, Neil W. Kowall, Leslie A. Shinobu, Jörg B. Schulz, Craig E. Thomas, Mark E. Gurney, M. Flint BealAbstract:Mutations in copper/zinc superoxide dismutase (SOD1) cause a subset of cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS). Transgenic mice that express these point mutations develop progressive paralysis and motor neuron loss thought to be caused by a gain-of-function of the enzyme. The gain-of-function may be an enhanced ability of the mutant SOD1 to generate .OH radicals or to facilitate peroxynitrite-mediated nitration of proteins. We found significant increases in concentrations of 3-Nitrotyrosine, a marker of peroxynitrite-mediated nitration, in upper and lower spinal cord and in cerebral cortex of transgenic mice with the FALS-associated G93A mutation. Malondialdehyde, a marker of lipid peroxidation, was increased in cerebral cortex. 3-Nitrotyrosine-, heme oxygenase-1-, and malondialdehyde-modified protein immunoreactivities were increased throughout SOD1 transgenic mice spinal cord but particularly within motor neurons. These results suggest that the gain-of-function of at least one mutant SOD1 associated with FALS involves increased protein nitration and oxidative damage, which may play a role in neuronal degeneration.
-
Increased 3-Nitrotyrosine in brains of Apo E-deficient mice
Brain Research, 1996Co-Authors: Russell T. Matthews, M. Flint BealAbstract:Apolipoprotein E (Apo-E) is linked to the pathogenesis of Alzheimer's disease. Apo-E deficient mice have increased lipid peroxidation in plasma. In the present study we examined two markers of oxidative stress in brains of Apo-E deficient mice. The ratios of 2,3 and 2,5 dihydroxybenzoic acid (DHBA)/salicylate, an index of hydroxyl radical generation, were unchanged except for an increase in 2,5-DHBA/salicylate in the cerebellum. 3-Nitrotyrosine is a marker for nitration of proteins produced by peroxynitrite. Concentrations of 3-Nitrotyrosine were significantly increased in the cerebral cortex, hippocampus, brainstem and cerebellum of Apo-E deficient mice. These results suggest the Apo-E may modulate oxidative stress produced by peroxynitrite.
