Proteomic identification of tyrosine nitration targets in kidney of spontaneously hypertensive rats

Tyther, Raymond; Ahmeda, Ahmad; Johns, Edward J.; Sheehan, David

doi:10.1002/pmic.200700503

Cited by 39 publications

(28 citation statements)

References 60 publications

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“…The medulla is an area that is significant in determining the level at which blood pressure may be set (7) and is a relatively hypoxic area and under oxidative stress (1). This is exacerbated in hypertension as demonstrated in recent proteomic studies in the medulla of the spontaneously hypertensive rat where there was enhanced nitration of proteins involved in NO signaling and antioxidant defense (22) as well as raised carbonylation of enolase 1 and catalase (23). Lenda and Boegehold (14) reported that exposure of rats to a high-salt diet resulted in a raised oxidant activity within the walls of arterioles in the skeletal microvasculature which they attributed to increased NAD(P)H oxidase activity (15).…”

mentioning

confidence: 90%

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Johns

O’Shaughnessy

O'Neill

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Pathophysiological states, including cardiovascular and renal diseases, are characterized by oxidative stress but what is less clear is whether physiological challenges incur a degree of altered oxidative metabolism. To this end, this study examined whether exposure to a high dietary sodium intake could cause an oxidative stress at the kidney. Animals, placed on either 0.3% or 3% sodium diets for 2 wk, were given a lethal dose of anesthetic, and kidneys were removed to analyze both NAD(P)H oxidase (NOX) and superoxide dismutase (SOD) expression and activities in the cortex and medulla. Placing animals on the highsodium diet raised sodium and water excretion and caused an ϳ14-fold increase in urinary excretion of 8-isoprostane, a marker of oxidative stress, which was attenuated by chronic treatment with apocynin to prevent NAD(P)H oxidase activity. The protein expression of the NAD(P)H oxidase subunits NOX2 and p47 phox and overall NAD(P)H oxidase activity were approximately doubled in the cortex of the rats on the high-sodium diet compared with those on the normal sodium intake while both SOD activity and expression were unchanged. By contrast, neither NOX nor SOD protein expression or activity were altered in the medulla when the rats were placed on the high-sodium intake. These data suggest that an elevation in dietary sodium intake can lead to increased generation of reactive oxygen species and a state of oxidative stress in the cortex but not to such a degree that it extends to the medulla. renal cortex; renal medulla; oxidative stress; nicotinamide adenine dinucleotide phosphate oxidase; superoxide dismutase THERE IS NOW A CLEAR consensus that, in many cardiovascular diseases, such as hypertension, heart failure, diabetes, and obesity, a state of oxidative stress exists where there is a raised production of reactive oxygen species that has potentially damaging effects on proteins, lipids, and DNA or react with nitric oxide (NO), thereby removing its functional role in physiological control mechanisms (17,20). Oxidative stress results from an imbalance between the generation of reactive oxygen species, such as superoxide anion (O 2 Ϫ ), hydrogen peroxide, and hydroxyl radical, and the antioxidant defense systems, such as superoxide dismutase (SOD) (18). NAD(P)H oxidases are responsible for the generation of reactive oxygen species, and in unstimulated phagocytes, where it was originally identified, the NAD(P)H oxidase enzyme is composed of gp91 phox , a membrane-integrated catalytic subunit associated with p22 phox , an accessory subunit. The activator (p67 phox ) and the organizer/adaptor subunits (p47 phox and p40 phox ) exist in the cytoplasm and, upon activation, translocate to the membrane to assemble the active oxidase that transfers electrons from the substrate to O 2 , forming O 2 Ϫ . Phagocytic gp91 phox [NAD(P)H oxidase (NOX) 2] has also been detected in vascular, cardiac, renal, and neural cells while its homolog NOX4 is abundant in the kidney and in vascular smooth muscle cells (6, 13). The activ...

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mentioning

confidence: 90%

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Johns

O’Shaughnessy

O'Neill

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…These reveal formation of carbonyl groups on residue side chains, tyrosine nitration and glutathionylation [11][12][13] [14,15]. Detection of redox-based modifications in this manner is arguably more informative than mere changes in protein abundance.…”

Section: Electrophoresis-based Detection Of Redox Lesionsmentioning

confidence: 99%

Redox proteomics

Sheehan¹,

Bárcena

2010

Expert Review of Proteomics

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“…Nitrated proteins may be identified in complex biological samples using 2D-PAGE in combination with western blotting with anti-nitrotyrosine antibodies and the identity of the proteins as well as the sites of modification determined by mass spectrometry (MS). However, only few actual nitration sites have been recognized using this approach [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Identification of Nitrotyrosine Containing Peptides using Combined Fractional Diagonal Chromatography (COFRADIC) and Off-Line Nano-LC-MALDI

Larsen

Bache

Gramsbergen

et al. 2011

J. Am. Soc. Mass Spectrom.

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Protein nitration take place on tyrosine residues under oxidative stress conditions and may influence a number of processes including enzyme activity, protein-protein interactions and phospho-tyrosine signalling pathways. Nitrated proteins have been identified in a number of diseases, however, the study of these proteins has been compromised by the lack of good methods for identifying nitrated proteins, their nitration sites and the level of nitration. Here, we present a method for identification of nitrated peptides that allows the site specific assignment of nitration, is easy to use and reproducible, and opens up for the possibility to quantify the level of nitration of specific peptides as function of different oxidative conditions, namely combined fractional diagonal chromatography (COFRADIC) in combination with off-line nano-LC-MALDI. We identify six nitrated peptides from in vitro nitrated bovine serum albumin and propose that automated COFRADIC using nano-LC and off-line MALDI-MS might be a possibility for identification of tyrosine nitrated proteins and the nitration sites in complex samples.

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Proteomic identification of tyrosine nitration targets in kidney of spontaneously hypertensive rats

Cited by 39 publications

References 60 publications

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Impact of elevated dietary sodium intake on NAD(P)H oxidase and SOD in the cortex and medulla of the rat kidney

Redox proteomics

Identification of Nitrotyrosine Containing Peptides using Combined Fractional Diagonal Chromatography (COFRADIC) and Off-Line Nano-LC-MALDI

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