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)

Interleukin-10 (IL-10) inhibited the production of superoxide anion (02-) by both unactivated and interferon-gamma (IFN-gamma)-activated human monocytes. Simultaneous addition of IL-10 with IFN-gamma at the start of incubation was necessary for an optimal inhibitory effect. The degree of inhibition was substantially comparable to that of IL-4, and the combination of suboptimal concentrations of IL-10 and IL-4 produced an additive effect. A similar effect was also obtained when viral IL-10 (vIL-10) was used instead of IL-10. The inhibitory effect of IL-10 was accompanied by the reduced accumulation of transcripts for heavy chain subunit of cytochrome b558 (gp9l-phox) and 47-kD cytosolic factor (p47-phox), components of the O2--generating NADPH oxidase system. Reduction of the mRNAs was distinct within 24 hours. On the other hand, the induced O2- production by human monocytic leukemia cell lines (THP-1 and HL60) was not inhibited by IL-10. The amount of gp9l-phox and p47-phox mRNAs remained unchanged even in the presence of excess amount of IL-1O. Taken together, these results suggest that IL-10 inhibits 02- production by downregulation of the gp9l-phox and p47-phox genes in human monocytes.
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PMID:Suppression of superoxide anion production by interleukin-10 is accompanied by a downregulation of the genes for subunit proteins of NADPH oxidase. 864 36

Acute promyelocytic leukemia (APL) cells are characterized by PML/RARalpha fusion protein, high responsiveness to arsenic trioxide (ATO)-induced cytotoxicity and an abundant generation of reactive oxygen species (ROS). In this study we investigated the association among these three features in APL-derived NB4 cells. We found that NADPH oxidase-derived ROS generation was more abundant in NB4 cells compared with monocytic leukemia U937 cells. By using PR9, a sub-line of U937 stably transduced with the inducible PML/RARalpha expression vectors, we attributed disparities on ROS generation and ATO sensitivity to the occurrence of PML/RARalpha fusion protein, since PML/RARalpha-expressing cells appeared higher NADPH oxidase activity, higher ROS level and higher sensitivity to ATO. On the other hand, the basal intensity of cAMP signaling pathway was compared between NB4 and U937 as well as between PR9 cells with or without PML/RARalpha, demonstrating that PML/RARalpha-expressing cells had an impaired cAMP signaling pathway which relieved its inhibitory effect on NADPH oxidase derived ROS generation. In summary, the present study demonstrated the correlation of PML/RARalpha with cAMP signaling pathway, NADPH oxidase and ROS generation in APL cells. PML/RARalpha that bestows NB4 cells various pathological features, paradoxically also endows these cells with the basis for susceptibility to ATO-induced cytotoxcity.
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PMID:PML/RARalpha fusion protein mediates the unique sensitivity to arsenic cytotoxicity in acute promyelocytic leukemia cells: Mechanisms involve the impairment of cAMP signaling and the aberrant regulation of NADPH oxidase. 1863 56

Influenza virus infection induces apoptosis and the expression of a set of pro-inflammatory cytokine genes, such as interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-beta and IFN-gamma, in cultured human fetal membrane chorion cells. Monocyte differentiation-inducing (MDI) activity in culture supernatants is simultaneously increased by the virus infection. The MDI activity is predominantly influenced by IL-6 molecule in culture supernatants, and partly by TNF-alpha and IFN-beta, but not IFN-gamma, molecules. The MDI factors are able to induce the mRNA expression of macrophage class A scavenger receptor (SR-A), which is one of adhesion and apoptotic cell-recognizing molecules, and gp91(phox), which is a catalytic subunit of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme complex, on monocytic cells. As a result, monocytes are initiated to differentiate into well-matured macrophages capable of adhering and producing superoxide through NADPH oxidase. The matured macrophages, obtained from human monocytic leukemia THP-1 cells by the treatment with MDI factors, phagocytose apoptotic chorion cell debris resulting from the virus infection. Subsequent to phagocytosis, an abrupt increase of superoxide production by macrophages may occur. In this article, we summarize recent knowledge about the MDI factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection, and discuss their possible pathological roles during pregnancy.
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PMID:Current status of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection. 1993 95