NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-α

Gertzberg, Nancy; Neumann, Paul; Rizzo, Victor; Johnson, A.

doi:10.1152/ajplung.00116.2003

Cited by 86 publications

(84 citation statements)

References 37 publications

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“…TNF-α induces NADPH oxidase-dependent superoxide production through several mechanisms, including increase in p22phox expression, and translocation of p47phox [37]. Our results have further revealed that TNF-α may activate the NADPH oxidase system by modulating the expression of Nox subunits.…”

Section: Discussionsupporting

confidence: 61%

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor‐α in human aortic smooth muscle and embryonic kidney cells

Moe

Aulia

Jiang

et al. 2006

J Cellular Molecular Medi

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Oxidative stress induced by superoxide (O 2¯⋅ ) and other reactive oxygen species (ROS) has critical roles in the pathogenesis of cardiovascular disease [1]. Potential enzymatic sources of ROS in vasculature include the mitochondrial respiration chain, lipoxygenase and cyclooxygenase, xanthine oxidase, NADPH oxidase, nitric oxide (NO) synthase and cytochrome P450 enzymes. Although our understanding of the mechanisms for superoxide production in vascular cells is incomplete, increasing evidence suggests that NADPH oxidase is a AbstractNADPH oxidases are important sources of vascular superoxide, which has been linked to the pathogenesis of atherosclerosis. Previously we demonstrated that the Nox4 subunit of NADPH oxidase is a critical catalytic component for superoxide production in quiescent vascular smooth muscle cells. In this study we sought to determine the role of Nox4 in superoxide production in human aortic smooth muscle cells (AoSMC) and embryonic kidney (HEK293) cells under proinflammatory conditions. Incubation with tumor necrosis factor-α (TNF-α, 10 ng/ml) for 12h increased superoxide production in both cell types, whereas angiotensin II, platelet-derived growth factor or interleukin-1β had little effects. Superoxide production was completely abolished by the NADPH oxidase inhibitors diphenyline iodonium and apocynin, but not by inhibitors of xanthine oxidase, nitric oxide synthase or mitochondrial electron transport. TNF-α upregulated the expression of Nox4 in AoSMC at both message and protein levels, while Nox1 and Nox2 were unchanged. In contrast, upregulation of Nox2 appeared to mediate the enhanced superoxide production by TNF-α in HEK293 cells. We suggest that Nox4 may be involved in increased superoxide generation in vascular smooth muscle cells under proinflammatory conditions.

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Section: Discussionsupporting

confidence: 61%

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor‐α in human aortic smooth muscle and embryonic kidney cells

Moe

Aulia

Jiang

et al. 2006

J Cellular Molecular Medi

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“…Plasma levels of platelet activating factor (PAF) are elevated in hypercholesterolemia [29], PAF is known to stimulate granulocytes to release cytokines such as TNF-α [30] which stimulates nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) in the endothelial cells to generate ROS [31] and INF-γ [32] which activate granulocytes to generate ROS [33]. In addition hypercholesterolemia increases synthesis of arachidonic acid and prostaglandins [34].…”

Section: Discussionmentioning

confidence: 99%

Antiatherosclerotic potential of aliskiren: its antioxidant and anti-inflammatory effects in rabbits: a randomized controlled trial

Al-Aubaidy¹,

Sahib²,

Mohammad³

et al. 2013

J Pharm Technol Drug Res

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Background: Aliskiren is a direct renin inhibitor. It counteracts renin-angiotensin system and is used to treat hypertension. This study aims to evaluate the effect of aliskiren on the progression of atherosclerosis in domestic rabbits. Methods: Twenty-one local domestic rabbits were divided into three groups each group had special dietary regimen for 8 weeks: Group I (normal control), Group II (atherogenic control) and Group III (2% Cholesterol + aliskiren 40mg/kg/day orally). Blood samples were collected at the end of experiment (8 weeks) for measurement of serum lipid profile, plasma high sensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA) and plasma reduced glutathione (GSH). Immunohistochemical analysis including vascular cell adhesion molecule-1 (VCAM-1); monocyte chemoattractant protein-1 (MCP-1); tumor necrotic factor -α (TNF-α); and interleukin -17 (IL-17). Histopathologic assessment of aortic atherosclerotic changes were also performed. Results: Compared to normal control group, there is a significant increase in the level of lipid profile, hs-CRP (134.1±1.2ug/L), and malondialdehyde (0.561±0.136umol/L) in the atherogenic diet group, while GSH was significantly reduced (0.58±0.024mmol/L) at (p ≤ 0.05). Immunohistochemical analysis showed that expression of aortic VCAM-1; MCP-1; TNF-α; and interleukin-17 were significantly increased in atherogenic control group compared to normal control group (p<0.001). In addition, animals on atherogenic diet have significant atherosclerotic lesion compared to normal control group. Aliskiren group appears to have no significant effect on lipid profile compared to atherogenic control group, but it has statistically significant reduction in hs-CRP (73.1±3.88ug/L) and MDA (0.261±0.15umol/L) at (p ≤ 0.05). Aliskiren treatment failed to significantly increase the level of plasma reduced glutathione. In addition, aliskiren treatment significantly reduced the expression of VCAM-1; MCP-1; TNF-α; and IL-17 (p≤0.05). Histopathological examination of aortic arch showed that aliskiren significantly reduced atherosclerotic lesion (p≤0.005). Conclusion: We can conclude that aliskiren is helpful in reducing lipid peroxidation, systemic inflammation and aortic expression of inflammatory markers used in this study and hence reduces the progression of atherosclerotic plague.

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“…68 Nevertheless, Rac1 activation also causes loss of cellcell contacts upon stimulation of endothelial cells with VEGF, PAF and TNF-a, as well as clustering of vascular cell adhesion molecule (VCAM)-1. 25,[69][70][71][72][73] These data seem to be conflicting; however, they in fact underlie the importance of understanding the particular GEFGTPase-effector complexes that are locally activated under resting and inflammatory conditions. We have summarized this in Figure 2.…”

Section: Endothelial Adherens Junction Control By Rho Gtpasesmentioning

confidence: 99%

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

Buul

Timmerman

2016

Small GTPases

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VE-cadherin-based cell-cell junctions form the major restrictive barrier of the endothelium to plasma proteins and blood cells. The function of VE-cadherin and the actin cytoskeleton are intimately linked. Vascular permeability factors and adherent leukocytes signal through small Rho GTPases to tightly regulate actin cytoskeletal rearrangements in order to open and re-assemble endothelial cell-cell junctions in a rapid and controlled manner. The Rho GTPases are activated by guanine nucleotide exchange factors (GEFs), conferring specificity and context-dependent control of cell-cell junctions. Although the molecular mechanisms that couple cadherins to actin filaments are beginning to be elucidated, specific stimulus-dependent regulation of the actin cytoskeleton at VEcadherin-based junctions remains unexplained. Accumulating evidence has suggested that depending on the vascular permeability factor and on the subcellular localization of GEFs, cell-cell junction dynamics and organization are differentially regulated by one specific Rho GTPase. In this Commentary, we focus on new insights how the junctional actin cytoskeleton is specifically and locally regulated by Rho GTPases and GEFs in the endothelium.

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NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-α

Cited by 86 publications

References 37 publications

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor‐α in human aortic smooth muscle and embryonic kidney cells

Differential upregulation of Nox homologues of NADPH oxidase by tumor necrosis factor‐α in human aortic smooth muscle and embryonic kidney cells

Antiatherosclerotic potential of aliskiren: its antioxidant and anti-inflammatory effects in rabbits: a randomized controlled trial

Small Rho GTPase-mediated actin dynamics at endothelial adherens junctions

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