ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes.

Monocytes play a key role in innate immunity by eliminating pathogens, releasing high levels of cytokines, and differentiating into several cell types, including macrophages and dendritic cells. Similar to other phagocytes, monocytes produce superoxide anions through the NADPH oxidase complex, which is composed of two membrane proteins (p22phox and gp91phox/NOX2) and four cytosolic proteins (p47phox, p67phox, p40phox and Rac1). The pathways involved in NADPH oxidase activation in monocytes are less known than those in neutrophils.

Activation of the phagocyte NADPH oxidase/NOX2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine.

Excessive reactive oxygen species (ROS) production can induce tissue injury involved in a variety of neurodegenerative disorders such as neurodegeneration observed in pilocarpine-induced temporal lobe epilepsy. Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist has beneficial effects in pilocarpine-induced temporal lobe epilepsy, when administered within minutes of seizure to avoid the harmful neurological lesions induced by pilocarpine. However, the enzymes involved in ROS productions and the effect of ketamine on this process remain less documented.

Phosphorylation of gp91/NOX2 in Human Neutrophils.

The phagocyte NADPH oxidase NOX2 was the first NOX family member to be discovered. It is responsible for the production of reactive oxygen species that are required for bacterial killing and host defense. Activated NOX2 is an enzymatic complex composed of two membrane proteins, p22 and gp91 (renamed NOX2), which form the cytochrome b, and four cytosolic proteins, p47, p67, p40, and the small GTPase Rac2.

NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions.

Inflammatory bowel disease (IBD) is characterized by severe and recurrent inflammation of the gastrointestinal tract, associated with altered patterns of cytokine synthesis, excessive reactive oxygen species (ROS) production, and high levels of the innate immune protein, lipocalin-2 (LCN-2), in the mucosa. The major source of ROS in intestinal epithelial cells is the NADPH oxidase NOX1, which consists of the transmembrane proteins, NOX1 and p22, and the cytosolic proteins, NOXO1, NOXA1, and Rac1. Here, we investigated whether NOX1 activation and ROS production induced by key inflammatory cytokines in IBD causally affects LCN-2 production in colonic epithelial cells.

NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells.

Dendritic cells (DCs) are a heterogeneous population of professional antigen-presenting cells and are key cells of the immune system, acquiring different phenotypes in accordance with their localization during the immune response. A subset of inflammatory DCs is derived from circulating monocytes (Mo) and has a key role in inflammation and infection. The pathways controlling Mo-DC differentiation are not fully understood.

Effect of lyophilized prune extract on hyperhomocysteinemia in mice.

Altered homocysteine metabolism defined as hyperhomocysteinemia is implicated as pathogenic factor in several cardiovascular diseases and atherosclerosis. The purpose of this study was to investigate the efficacy of prune extract, a good source of phenolic antioxidants, on lowering plasma homocysteine level in male hyperhomocysteinemic mice from average weight of 28 g. The administration of lyophilized prune extract was carried out by intraperitoneal injection one day preceding and one hour before sacrifice of mice.

DYRK1A overexpression decreases plasma lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels.

Background And Aims: Down syndrome is caused by trisomy of all or part of human chromosome 21. Individuals with Down syndrome present some metabolic abnormalities involving lipoproteins, notably lower high-density lipoprotein levels associated with altered lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels. DYRK1A is a kinase overexpressed in Down syndrome that can activate the STAT3 pathway, which is involved in lecithin:cholesterol acyltransferase expression.

Hepatocyte-specific Dyrk1a gene transfer rescues plasma apolipoprotein A-I levels and aortic Akt/GSK3 pathways in hyperhomocysteinemic mice.

Hyperhomocysteinemia, characterized by high plasma homocysteine levels, is recognized as an independent risk factor for cardiovascular diseases. The increased synthesis of homocysteine, a product of methionine metabolism involving B vitamins, and its slower intracellular utilization cause increased flux into the blood. Plasma homocysteine level is an important reflection of hepatic methionine metabolism and the rate of processes modified by B vitamins as well as different enzyme activity.

BDNF and DYRK1A are variable and inversely correlated in lymphoblastoid cell lines from Down syndrome patients.

Down syndrome or trisomy 21 is the most common genetic disorder leading to mental retardation. One feature is impaired short- and long-term spatial memory, which has been linked to altered brain-derived neurotrophic factor (BDNF) levels. Mouse models of Down syndrome have been used to assess neurotrophin levels, and reduced BDNF has been demonstrated in brains of adult transgenic mice overexpressing Dyrk1a, a candidate gene for Down syndrome phenotypes.

Dyrk1a activates antioxidant NQO1 expression through an ERK1/2-Nrf2 dependent mechanism.

Background And Aims: Among cardiovascular risk factor, people with Down syndrome have a lower plasma homocysteine level. In a previous study, we have shown that DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1a), a serine/threonine kinase found on human chromosome 21, is implicated on homocysteine metabolism regulation. Indeed, mice that overexpress in liver this kinase have a lower plasma homocysteine level concomitant with an increased hepatic S-adenosyhomocysteine hydrolase (SAHH) activity, which depends on the activation of NAD(P)H:quinone oxidoreductase-1 (NQO1).

Stable accumulation of p67phox at the phagosomal membrane and ROS production within the phagosome.

Production of ROS by the leukocyte NADPH oxidase is essential for the destruction of pathogenic bacteria inside phagosomes. The enzyme is a complex of cytosolic and membranous subunits that need to assemble upon activation. Biochemical data suggest that the complex is renewed continuously during activity.

Kinetic analysis of phagosomal production of reactive oxygen species.

Phagocytes produce large quantities of reactive oxygen species for pathogen killing; however, the kinetics and amplitude of ROS production on the level of individual phagosomes are poorly understood. This is mainly due to the lack of appropriate methods for quantitative ROS detection with microscopic resolution. We covalently attached the ROS-sensitive dye dichlorodihydrofluorescein (DCFH(2)) to yeast particles and investigated their fluorescence due to oxidation in vitro and in live phagocytes.

Amiloride derivatives modulate PS externalization in neutrophil-like PLB-985 cells.

During brain or cardiac ischemia/reperfusion neutrophils are recruited and activated contributing to inflammation and tissue damage. Neutrophils are removed from inflamed tissues by phosphatidylserine-dependent phagocytosis. Production of reactive oxygen species by the neutrophil NADPH-oxidase is known to affect phosphatidylserine externalization.