Dominant mutations in p97/VCP (valosin-containing protein) cause a rare multisystem degenerative disease with varied phenotypes that include inclusion body myopathy, Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. p97 disease mutants have altered N-domain conformations, elevated ATPase activity, and altered cofactor association. We have now discovered a prev...

Respiratory burst activity and phosphorylation of an NADPH oxidase component, p47(phox), during neutrophil stimulation are mediated by phosphatidylinositol 3-kinase (PI-3K) activation. Products of PI-3K activate several kinases, including the serine/threonine kinase Akt. The present study examined the ability of Akt to regulate neutrophil respiratory burst activity and to interact with and phos...

The NADPH oxidase of human monocytes is activated upon exposure to opsonized zymosan and a variety of other stimuli to catalyze the formation of superoxide anion. Assembly of the NADPH oxidase complex is believed to be a highly regulated process, and molecular mechanisms responsible for this regulation have yet to be fully elucidated. We have previously reported that cytosolic phospholipase A(2...

Experimental animals placed on a high-cholesterol diet for 2 or more weeks exhibit an inflammatory response in postcapillary venules. The aims of this study were to determine (1) whether superoxide mediates the hypercholesterolemia-induced inflammatory response and (2) whether leukocyte and/or vessel wall NAD(P)H oxidase contributes to this response. Intravital videomicroscopy was used to quant...

presented in this issue lies as much in the questions it raises as in those it answers. In setting out to prove that p47, a regulatory subunit of the phagocyte NADPH oxidase, is equally vital to the superoxide-generating enzyme of vascular endothelial cells, which they successfully did, they also turned up a number of unexpected observations. The latter results, whose interpretation will necess...

It has been hypothesized that O(2) sensing in type I cells of the carotid body and erythropoietin (EPO)-producing cells of the kidney involves protein components identical to the NADPH oxidase system responsible for the respiratory burst of phagocytes. In the present study, we evaluated O(2) sensing in mice with null mutant genotypes for two components of the phagocytic oxidase. Whole body plet...

DiStasi MR, Unthank JL, Miller SJ. Nox2 and p47 modulate compensatory growth of primary collateral arteries. Am J Physiol Heart Circ Physiol 306: H1435–H1443, 2014. First published March 14, 2014; doi:10.1152/ajpheart.00828.2013.—The role of NADPH oxidase (Nox) in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxyg...

Accumulating evidence suggests a critical role of increased reactive oxygen species production for left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). An increased myocardial activity of the NAD(P)H oxidase, a major oxidant enzyme system, has been observed in human heart failure; however, the role of the NAD(P)H oxidase for LV remodeling and dysfunction after MI r...

BACKGROUND INFORMATION During phagocytosis, neutrophils internalise pathogens in a phagosome and produce reactive oxygen species (ROS) by the NADPH oxidase to kill the pathogen. The cytosolic NADPH oxidase subunits p40(phox), p47(phox), p67(phox) and Rac2 translocate to the phagosomal membrane to participate in enzyme activation. The kinetics of this recruitment and the underlying signalling pa...

We recently showed that mRNA levels coding the highaffinity Fcy receptor for IgG (FcyR-I, CD64) and two of the components of the phagocytic superoxide anion-generating system-the heavy-chain subunit of cytochrome b, , (gp91phox) and the 47-Kd cytosolic factor (p47-phox)-are modulated by interferon gamma (IFN-y). In this study, we examined whether dexamethasone (DEX) affects gp9l-phox and p47-ph...