Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.3.1 (
NADPH oxidase
)
11,281
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) and nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase p22phox are linked with the expression and/or progression of vascular disease. We hypothesized that these polymorphisms may influence the development and/or progression of systemic lupus erythematosus (SLE), given their linkage with vascular disease. DNA from patients with SLE (n = 90) and their age- and sex-matched controls (n = 86) from The Second Xiangya Hospital of Central South University was assessed for eNOS and
NADPH oxidase
p22phox polymorphisms. These polymorphisms were examined by restriction fragment length polymorphism-polymerase chain reaction. The allele frequency of the
NADPH oxidase
p22phox gene C242T polymorphisms significantly varied between the SLE patients and the controls. We found no association of the eNOS polymorphism with the development of renal disease. These results indicated that the etiology of patients with SLE is associated with
NADPH oxidase
p22phox gene C242T polymorphisms. There was no significant increased risk of SLE associated with eNOS polymorphisms in the Chinese population.
Lupus
2010 Feb
PMID:Endothelial nitric oxide synthase and nicotinamide adenosine dinucleotide phosphate oxidase p22phox gene (C242T) polymorphisms and systemic lupus erythematosus in a Chinese Population. 1996 45
The phagocyte
NADPH oxidase
(the NOX2 complex) generates superoxide, the precursor to reactive oxygen species (ROS). ROS possess both antimicrobial and immunoregulatory function. Inactivating mutations in alleles of the NOX2 complex cause chronic granulomatous disease (CGD), characterized by an enhanced susceptibility to infections and autoimmune diseases such as Systemic lupus erythematosus (SLE). The latter is characterized by insufficient removal of dead cells, resulting in an autoimmune response against components of the cell's nucleus when non-cleared apoptotic cells lose their membrane integrity and present autoantigenic molecules in an inflammatory context. Here we aimed to shed light on the role of the NOX2 complex in handling of secondary necrotic cells (SNECs) and associated consequences for inflammation and autoimmunity during lupus. We show that individuals with SLE and CGD display accumulation of SNECs in blood monocytes and neutrophils. In a CGD phenotypic mouse strain (Ncf1** mice) build-up of SNECs in Ly6C
HI
blood monocytes was connected with a delayed degradation of the phagosomal cargo and accompanied by production of inflammatory mediators. Treatment with H
2
O
2
or activators of ROS-formation reconstituted phagosomal abundance of SNECs to normal levels. Induction of experimental lupus further induced increased antibody-dependent uptake of SNECs into neutrophils.
Lupus
-primed Ncf1** neutrophils took up more SNECs than wild type neutrophils, whereas SNEC-accumulation in regulatory Ly6C
-/LO
monocytes was lower in Ncf1**mice. We deduce that the inflammatory rerouting of immune-stimulatory necrotic material into inflammatory phagocyte subsets contributes to the connection between low ROS production by the NOX2 complex and SLE.
...
PMID:NOX2 mediates quiescent handling of dead cell remnants in phagocytes. 3134 19
