Increased nitric oxide production accompanied by the up‐regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus

Hm, Belmont; Levartovsky, David; Goel, Aditya; Amin, Ashok R.; Giorno, Ralph; Rediske, John; Ml, Skovron; Abramson, Steven B.

doi:10.1002/art.1780401013

Cited by 145 publications

(92 citation statements)

References 25 publications

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“…NO mediates DNA damage by three mechanisms. It has been reported that NO production is increased in patients with Systemic lupus erythematosus (SLE) [31]. The disorder is characterized by immune activated state where Inducible nitric oxide synthase (iNOS) level is increased in tissues like macrophages, splenic and renal tissues and consequently NO production [32].…”

Section: Direct Effect Of Nomentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from L-arginine by converting it to L-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating many of the genotoxic/ carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide using both selective or specific nitric oxide synthase inhibitor or nonselective nitric oxide synthase inhibitor with respect to isoforms of nitric oxide.Keywords Nitric oxide Á Nitric oxide synthase Á Nitric oxide inhibitors Á Generation of nitric oxide Á Cancer Á Systemic lupus erythematosus Á Direct and indirect effect of nitric oxide Á Effect of nitric oxide on mitochondria

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Section: Direct Effect Of Nomentioning

confidence: 99%

Biochemistry of Nitric Oxide

2011

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“…However, MRL/lpr iNOS knockout mice develop renal disease similar to the wild-type animal [64]. Belmont and colleagues reported elevated serum nitrite levels, an in vivo marker of NO production, in lupus patients [65,66]. Serum nitrite levels correlated with disease activity and anti-DNA antibody levels.…”

Section: Nitric Oxide Induced Mitochondrial Biogenesis Mediated Altermentioning

confidence: 99%

The role of nitric oxide in abnormal T cell signal transduction in systemic lupus erythematosus

Nagy

Perl

2006

Clinical Immunology

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by production of antinuclear autoantibodies and diverse array of clinical manifestations. T cells from patients with SLE have been shown to be activated in vivo and provide help to autoreactive B cells. Lupus T cells exhibit enhanced spontaneous and diminished activation-induced apoptosis and predisposition to necrosis. Persistent mitochondrial hyperpolarization and ATP depletionassociated with significantly increased mitochondrial mass -characterize T lymphocyte dysfunction in SLE. In addition to cell death abnormalities, mitochondrial dysfunction is associated with altered signal transduction through the T cell receptor and Ca 2+ fluxing. Exposure of normal T cell to nitric oxide induces mitochondrial hyperpolarization and biogenesis and regenerates the Ca 2+ signaling profile of lupus T cells. This article reviews a novel understanding of the role of nitric oxide in signal transduction and cell death abnormalities in SLE.

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“…Nitric oxide synthesised by endothelial nitric oxide synthase (eNOS) has vasodilatory effects on vascular tone, inhibits platelet aggregation, and modulates smooth muscle proliferation [10]. Overproduction of NO could contribute to tissue injury, given its capacity to increase vascular permeability, generate toxic free radicals, such as peroxynitrite, and induce cytotoxicity [11]. Deficiency of the NOS3 gene leads to reduced bone formation and impaired osteoblast function [12].…”

Section: Introductionmentioning

confidence: 99%