Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophil disfunction, caused by a decreased production of effective radical oxygen species by myeloperoxidase (MPO) and NADPH oxidase within the neutrophil, may result in susceptibility to opportunistic fungal infections. In vitro, MPO produces OCl, which kills bacteria and viruses. In the case of MPO deficiency, susceptibility to Candida albicans infection was observed. Furthermore, it was demonstrated that MPO knockout mice were primarily susceptible to C. albicans infection. With regards to NADPH oxidase deficiency, such a patient was found to have severe chronic granulomatous disease (CGD) due to Aspergillus infection. This deficiency may have resulted from a gene mutation and/or abnormality of the NADH oxidase components, particularly cytochrome b558 (gp91phox and p22phox) in membrane and cytosol factors p47phox, p67phox, p40phox and others in neutrophil. Thus,irregular regulation of transcription factors for gene expression of phox molecules and MPO permits susceptibility to Aspergillus and Candida infections.
 ...
PMID:[Contribution of neutrophils to Aspergillus infection]. 1214 29

Neutrophil granule exocytosis is crucial for host defense and inflammation. Neutrophils contain 4 types of granules, the exocytotic release of which is differentially regulated. This exocytosis is known to be driven by diverse mediators, including calcium and nucleotides, but the precise molecular mechanism remains largely unknown. We show in the present study that voltage-gated proton (Hv) channels are necessary for the proper release of azurophilic granules in neutrophils. On activation of NADPH oxidase by PMA and IgG, neutrophils derived from Hvcn1 gene knockout mouse exhibited greater secretion of MPO and elastase than WT cells. In contrast, release of LTF enriched in specific granules was not enhanced in these cells. The excess release of azurophilic granules in Hv1/VSOP-deficient neutrophils was suppressed by inhibiting NADPH oxidase activity and, in part, by valinomycin, a potassium ionophore. In addition, Hv1/VSOP-deficient mice exhibited more severe lung inflammation after intranasal Candida albicans infection than WT mice. These findings suggest that the Hv channel acts to specifically dampen the release of azurophilic granules through, in part, the suppression of increased positive charges at the plasma membrane accompanied by the activation of NADPH oxidase in neutrophils.
...
PMID:The voltage-gated proton channel Hv1/VSOP inhibits neutrophil granule release. 2673