Peroxynitrite mediates TNF-α-induced endothelial barrier dysfunction and nitration of actin

Neumann, Paul; Gertzberg, Nancy; Vaughan, Erin E; Weisbrot, Joshua; Woodburn, Renee; Lambert, W. Marcus; Johnson, A.

doi:10.1152/ajplung.00391.2005

Cited by 52 publications

(64 citation statements)

References 41 publications

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“…For example, during iNOS induction, NO reacts with oxygen or superoxide to produce RNS that can initiate protein oxidation, lipid oxidation, and DNA damage (24,25). One RNS, peroxynitrite (ONOO Ϫ ), is formed from the chemical reaction between NO and superoxide (26) and can damage not only membranes but also nitrate protein tyrosine and change the activities of a number of important enzymes (27,28). Moreover, decreased capillary perfusion can lead to parenchymal hypoxia (29) and superoxide generation to fuel RNS synthesis (30).…”

Section: Discussionmentioning

confidence: 99%

Evidence for the Role of Reactive Nitrogen Species in Polymicrobial Sepsis-Induced Renal Peritubular Capillary Dysfunction and Tubular Injury

Wu¹,

Gökden²,

Mayeux³

2007

Journal of the American Society of Nephrology

123

133

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Acute kidney injury (AKI) remains a frequent and serious complication of human sepsis that contributes significantly to mortality. For better understanding of the development of AKI during sepsis, the cecal ligation and puncture (CLP) murine model of sepsis was studied using intravital video microscopy (IVVM) of the kidney. IVVM with FITC-dextran was used to determine the percentage of capillaries with continuous, intermittent or no flow at 0 (sham), 10, 16, and 22 h after CLP. There was a dramatic fall in capillary perfusion as early as 10 h after CLP that persisted through 22 h. The percentage of vessels with continuous flow at 16 h decreased from 73 ؎ 2% in shams to 16 ؎ 2% (P < 0.05), whereas the percentage of vessels with no flow increased from 4 ؎ 1% in shams to 42 ؎ 2% (P < 0.05). The capillary perfusion defect preceded the rise in serum creatinine. IVVM with dihydrorhodamine-123 was used to quantify in real time reactive nitrogen species (RNS) generation by renal tubules, and the inducible nitric oxide synthase inhibitor L-iminoethyl-lysine (mg/kg) was used to examine the role of inducible nitric oxide synthase inhibitor on capillary dysfunction and RNS generation. Tubular generation of RNS was significantly elevated at 10 h after CLP and was associated with tubules that were bordered by capillaries with reduced perfusion. L-Iminoethyl-lysine significantly reversed the capillary perfusion defect, blocked RNS generation, and reduced AKI. These data show that capillary dysfunction and RNS generation contribute to tubular injury and suggest that RNS should be considered a potential therapeutic target in the treatment of sepsis-induced AKI.

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Section: Discussionmentioning

confidence: 99%

Evidence for the Role of Reactive Nitrogen Species in Polymicrobial Sepsis-Induced Renal Peritubular Capillary Dysfunction and Tubular Injury

Wu¹,

Gökden²,

Mayeux³

2007

Journal of the American Society of Nephrology

123

133

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“…PMEM were treated with TNF at 100 ng/ml (from a stock solution of 10 g/ml), a dose that induces a consistent permeability increase (13,23). Gö6976, a selective inhibitor of cPKC (26), and SB-216763, a selective inhibitor of GSK3␤ that blocks the GSK3␤ binding site for ATP (3,9), were obtained from BIOMOL International (Plymouth Meeting, PA).…”

Section: Reagentsmentioning

confidence: 99%

“…In pulmonary microvessel endothelial cells, this laboratory demonstrated TNF causes a PKC␣-mediated barrier dysfunction associated with dislocation of ␤-catenin from ␤-actin within the zonular adherence (10,12,18,23). Thus, the dislocation of ␤-catenin may result in genomic activity of ␤-catenin that can be modulated by GSK3␤ activity (1,4,5,15,25).…”

mentioning

confidence: 99%

TNF-induced activation of pulmonary microvessel endothelial cells: a role for GSK3β

Johnson

2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Nitration of α-tubulin significantly alters microtubule formation and structure during ischemic conditions (77). Actin contains many tyrosine residues critical to actin polymerization, and nitration of actin induces stabilization of actin nucleus and filament formation, resulting in the contractile dysfunction of cardiomyocytes (78).…”

Section: Protein Tyrosine Nitration Under Pathophysiological Statesmentioning

confidence: 99%

Nitrosative protein tyrosine modifications: biochemistry and functional significance

Yeo

Lee²,

Lee³

et al. 2008

BMB Reports

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Nitrosative modifications regulate cellular signal transduction and pathogenesis of inflammatory responses and neurodegenerative diseases. Protein tyrosine nitration is a biomarker of oxidative stress and also influences protein structure and function. Recent advances in mass spectrometry have made it possible to identify modified proteins and specific modified amino acid residues. For analysis of nitrated peptides with low yields or only a subset of peptides, affinity 'tags' can be bait for 'fishing out' target analytes from complex mixtures. These tagged peptides are then extracted to a solid phase, followed by mass analysis. In this review, we focus on protein tyrosine

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Peroxynitrite mediates TNF-α-induced endothelial barrier dysfunction and nitration of actin

Abstract: son. Peroxynitrite mediates TNF-␣-induced endothelial barrier dysfunction and nitration of actin.

Cited by 52 publications

References 41 publications

Evidence for the Role of Reactive Nitrogen Species in Polymicrobial Sepsis-Induced Renal Peritubular Capillary Dysfunction and Tubular Injury

Evidence for the Role of Reactive Nitrogen Species in Polymicrobial Sepsis-Induced Renal Peritubular Capillary Dysfunction and Tubular Injury

TNF-induced activation of pulmonary microvessel endothelial cells: a role for GSK3β

Nitrosative protein tyrosine modifications: biochemistry and functional significance

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