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:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intense immunoreactivity for the m2-muscarinic receptor was found in a population of interstitial polymorphic neurons embedded within the infracortical white matter and the adjacent deep layers of the cerebral cortex. These infracortical neurons were evenly distributed throughout architectonic subdivisions of the monkey cortex except for parts of primary visual cortex where they were less numerous. A similar set of m2-immunoreactive interstitial cells was also detected in the human lateral temporal neocortex obtained at surgery. Upon electron microscopic examination, they were found to receive unlabelled synaptic inputs and displayed abundant rough endoplasmic reticulum, a prominent nucleolus, and invaginations of the nuclear membrane. Double labelling of m2 immunoreactivity and acetylcholinesterase histochemistry demonstrated that approximately 90% of the m2-positive infracortical cells were acetylcholinesterase-rich in the monkey and human brains. Conversely, the proportion of acetylcholinesterase-rich infracortical neurons that were m2-immunoreactive was over 90% in the monkey and at least 50% in the human. The concurrent visualization of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) enzyme activity with m2 immunoreactivity in the monkey and human brain showed that 85-95% of m2-immunoreactive infracortical cells were NADPH-d positive. Conversely, about 70% of NADPH-d cells contained m2 immunoreactivity. These observations provide the most convincing information to date that many of the acetylcholinesterase-rich neurons located in the infracortical white matter of the cerebral cortex are likely to be cholinoceptive. The expression of NADPH-d by these neurons suggests that they may also provide a relay through which cholinergic innervation, originating predominantly from the nucleus basalis of Meynert, could regulate the release of nitric oxide in the cerebral cortex and subjacent white matter. The degeneration of these neurons may account for at least some of the depletion of m2 receptors that has been reported in Alzheimer's disease.
...
PMID:Infracortical interstitial cells concurrently expressing m2-muscarinic receptors, acetylcholinesterase and nicotinamide adenine dinucleotide phosphate-diaphorase in the human and monkey cerebral cortex. 957 81

Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry was used to demonstrate the presence of nitric oxide in the developing chicken thymus. NADPH-d was first expressed in the epithelial cells located at the corticomedullary junction of the thymic rudiment on day 13 of incubation. The number of labelled cells gradually increased from day 13 to day 21. Ultrastructural evidence showed that the labelling was localized in a heterogeneous population of cells in the medulla near the corticomedullary junction, comprising the cystic, undifferentiated, myoid, lymphoid and epithelial reticular cells. At this age, the vascular endothelium was NADPH-d positive. Labelling was also detected in some macrophages. The reaction product primarily labelled profiles of rough endoplasmic reticulum and to a lesser extent the outer membranes of mitochondria, portions of the nuclear envelope and the Golgi apparatus. By day 18/19, NADPH-d-labelled nerve fibres were occasionally observed in the interlobular connective tissue. By day 21, these fibres formed perivascular plexuses. Labelled nerve fibres were occasionally observed in the medullary parenchyma. Possible functions of nitric oxide in the embryonic thymus are discussed.
...
PMID:Ontogeny of NADPH-d expression in the thymic microenvironment of the chick embryo. 979 49

This study examined the distribution of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reactivity and nitric oxide synthase (NOS) immunoreactivity in the lumbosacral dorsal root ganglia (DRG) in male guinea pigs. A differential distribution of NADPH-d reactivity and NOS immunoreactivity was detected in neurons of DRG at different segmental levels. There were numerically more intensely stained NADPH-d and NOS reactive cells in the rostral (L1-L3) DRG compared with those at the caudal (L6-S4) levels. In the corresponding DRG, NADPH-d reactivity was not paralleled by NOS immunoreactivity. This was evidenced by the wide distribution of afferent neurons in the lumbosacral DRG stained for NADPH-d, yet only a small number of them exhibited NOS immunoreactivity. Double labelling study has shown that some of the NADPH-d positive neurons were NOS negative. Ultrastructurally, NADPH-d reaction product was associated with the membranes of various subcellular organelles, including the rough endoplasmic reticulum (rER), Golgi saccules, mitochondria and some segments of the nuclear envelop, whereas NOS immune-precipitate was patchily distributed throughout the cytoplasm. Present results suggest that nitric oxide (NO) may function as a neurotransmitter in the afferent pathways at lumbosacral segments. On the other hand, in view of their marked disparity in numbers and the lack of total one-to-one correspondence, it seems likely that the NOS positive neurons represent only a subpopulation of the NADPH-d positive cells in the lumbosacral DRG.
...
PMID:Localization of nicotinamide adenine dinucleotide phosphate-diaphorase reactivity and nitric oxide synthase immunoreactivity in the lumbosacral dorsal root ganglia in guinea pigs. 1002 35

We investigated the subcellular localization of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity, a histo- and cyto-chemical marker of nitric oxide synthase, in human placental trophoblast obtained from women with normal term pregnancies. Tetrazolium salt BSPT was used as the capturing agent. Precipitates of BSPT-formazan indicative of NADPH-d reaction were observed on the membranes of endoplasmic reticulum and nuclear envelope of syncytiotrophoblasts. Our results indicate these two intracytoplasmic organellae are the sites of nitric oxide generation in the syncytiotrophoblasts of normal term human placenta.
...
PMID:Enzyme-cytochemically detectable NADPH-diaphorase activity is present in the endoplasmic reticulum and nuclear envelope of the syncytiotrophoblast of the human placenta. 1056 58

The cellular and subcellular distribution of neuronal nitric oxide synthase and its related reduced beta-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was compared in wild-type and homozygous knockout mice, in which the gene for neuronal nitric oxide synthase has been disrupted, resulting in a lack of the predominant splice isoform alpha. In the laterodorsal tegmental nucleus, used as a model structure, the cholinergic principal neurons also exhibited an intensive neuronal nitric oxide synthase immunoreactivity. Using the tetrazolium salt 2-(2-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)-tetrazo++ +-lium chloride (BSPT), these neurons were filled with NADPH-diaphorase reaction product, whereas the equivalent neurons of knockout mice showed, if at all, only traces of neuronal nitric oxide synthase immunoreactivity in parallel to a diminished NADPH-diaphorase labelling. Subcellularly, the neuronal nitric oxide synthase-related diaminobenzidine product was, apparently owing to diffusion artifact, more or less evenly distributed in the cytosol of the neuronal perikarya and dendrites of wild-type mice. In contrast, the BSPT reaction product formazan was closely and discretely attached to endocellular membranes. In the intensely NADPH-diaphorase stained neurons of wild-type mice, 85% of the mitochondria were, at least partly, labelled for BSPT-formazan, whilst in the equivalent neurons of mutant mice, only 13% of mitochondria were NADPH-diaphorase positive. Related to the NADPH-diaphorase activity in the principal neurons of wild-type mice, only 10% of membranes of the endoplasmic reticulum, 27% of mitochondrial membranes and 26% of the nuclear envelope exhibited NADPH-diaphorase activity in the mutant mice. Our findings with the BSPT histochemistry suggest that residues of NADPH-diaphorase positivity in mutant mice are attributed to the alternative splice isoforms beta and/or gamma of neuronal nitric oxide synthase. The splice isoform a is located predominantly at the membranes of the endoplasmic reticulum.
...
PMID:Ultrastructural localization of neuronal nitric oxide synthase in the laterodorsal tegmental nucleus of wild-type and knockout mice. 1061 9

Matrix GLA protein (MGP) is an inhibitor of calcification in the arterial wall and its activity is dependent upon vitamin K-dependent gamma-carboxylation. This modification is carried out by a warfarin sensitive enzyme system that converts specific Glu residues to gamma-carboxyglutamic acid (GLA) residues. Recent studies have demonstrated that the gamma-carboxylation system in the arterial wall, in contrast to that in the liver, is unable to use vitamin K as an antidote to warfarin. By use of immunohistochemistry we demonstrate that MGP is expressed in the arterial wall and immunocytochemistry localized the MGP precursors to the endoplasmic reticulum in vascular smooth muscle cells. Resting smooth vascular muscle cells in the aortic wall and proliferating cells from explants of the aorta have all the enzymes needed for gamma-carboxylation of MGP. However, when compared to the liver system, expression of the enzymes of the gamma-carboxylation system in vascular smooth muscle cells is different. Of particular interest is the finding that the specific activity of the warfarin sensitive enzyme vitamin K epoxide reductase is 3-fold higher in vascular smooth muscle cells than in liver. DT-diaphorase, which catalyses the antidotal pathway for vitamin K reduction in liver, is 100-fold less active in resting vascular smooth muscle cells than in liver. Data obtained from an in vitro gamma-carboxylation system suggest that the antidotal pathway catalyzed by DT-diaphorase in the vessel wall is unable to provide the carboxylase with enough reduced vitamin K to trigger gamma-carboxylation of MGP. This finding provides an explanation to the inability of vitamin K to work as an antidote to warfarin intoxication of the arterial wall. Therefore the vitamin K dependent gamma-carboxylation system in the arterial wall share a common feature with the system in bone cells by being unable to utilize vitamin K as an antidote.
...
PMID:Matrix Gla protein synthesis and gamma-carboxylation in the aortic vessel wall and proliferating vascular smooth muscle cells--a cell system which resembles the system in bone cells. 1061 67

It has recently been suggested that, in addition to nitric oxide (NO), carbon monoxide (CO) is an important gaseous messenger which might be involved in vertebrate olfactory transduction because its effects include activation of guanylyl cyclase and the formation of cGMP. As there is no information regarding the presence of heme oxygenase-2 -- the constitutive isoform of the heme oxygenase system -- in olfactory neurons of non-rodent species, we have investigated the distribution pattern of heme oxygenase-2 in the olfactory epithelium of the bovine, a representative of macrosmatics. Localization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity of the olfactory epithelium was compared with heme oxygenase-2 and NO synthase (NOS) immunoreactivities in order to obtain possible hints at functional significance. NADPH-d activity was particularly intense in apical dendrites of receptor neurons. It was also found in Bowman glands and intraepithelial duct cells. Less intense, discrete NADPH-d activity was present also at intermediate and basal levels of the olfactory epithelium, corresponding to the layer of receptor neuron somata and basal cells. While heme oxygenase-2 activity mainly occurred in neuronal perikarya, a very intense NOS immunoreactivity, exclusively for the inducible isoform, was detected in the apical dendrites. Ultrastructurally, NADPH-d histochemistry showed distinct labelling of membranes, in particular of endoplasmic reticulum, mitochondria and nucleus. The coincident localization of the moderate NADPH-d activity and heme oxygenase-2 immunoreactivity in receptor cell perikarya suggest a functional association between NADPH-cytochrome P450 reductase and heme oxygenase-2. In contrast, dendritic localization of NADPH-d activity is topically and possibly functionally related to the presence of the inducible isoform of NOS. The results suggest that both CO and NO may be generated in bovine receptor neurons and thus involved in odorant stimulation. Based on immunocytochemical localization of synthesizing enzymes, NO might be regarded as a direct regulator of transduction related processes while CO might act as a modulator of the initial signal.
...
PMID:Heme oxygenase-2 and nitric oxide synthase immunoreactivity of bovine olfactory receptor neurons and a comparison with the distribution of NADPH-diaphorase staining. 1094 53

beta-Lapachone (beta-Lap) triggers apoptosis in a number of human breast and prostate cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. Downstream signaling pathway(s) that initiate apoptosis following treatment with beta-Lap have not been elucidated. Since calpain activation was suspected in beta-Lap-mediated apoptosis, we examined alterations in Ca(2+) homeostasis using NQO1-expressing MCF-7 cells. beta-Lap-exposed MCF-7 cells exhibited an early increase in intracellular cytosolic Ca(2+), from endoplasmic reticulum Ca(2+) stores, comparable to thapsigargin exposures. 1,2-Bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, an intracellular Ca(2+) chelator, blocked early increases in Ca(2+) levels and inhibited beta-Lap-mediated mitochondrial membrane depolarization, intracellular ATP depletion, specific and unique substrate proteolysis, and apoptosis. The extracellular Ca(2+) chelator, EGTA, inhibited later apoptotic end points (observed >8 h, e.g. substrate proteolysis and DNA fragmentation), suggesting that later execution events were triggered by Ca(2+) influxes from the extracellular milieu. Collectively, these data suggest a critical, but not sole, role for Ca(2+) in the NQO1-dependent cell death pathway initiated by beta-Lap. Use of beta-Lap to trigger an apparently novel, calpain-like-mediated apoptotic cell death could be useful for breast and prostate cancer therapy.
...
PMID:Calcium is a key signaling molecule in beta-lapachone-mediated cell death. 1127 25

NAD(P)H:quinone oxidoreductase 1 (NQO1) is implicated in both chemoprevention and bioactivation of DNA-damaging antitumor agents. NQO1 is mainly cytosolic, but distribution in other cellular compartments, particularly in tumor cells, is poorly defined. Nuclear NQO1 in HT29 human colon carcinoma and H661 human non-small cell lung cancer cells was observed using both confocal microscopy and immunoelectron microscopy. NQO1 was not detected in mitochondria, golgi, or endoplasmic reticulum. In addition, purified intact nuclei from HT29 cells contained immunoreactive NQO1, which was catalytically active as determined by conventional activity assay. In summary, we have confirmed the presence of nuclear NQO1, which has implications for chemoprotection and bioactivation of DNA-damaging antitumor agents.
...
PMID:Subcellular localization of NAD(P)H:quinone oxidoreductase 1 in human cancer cells. 1188 14

Beta-lapachone (beta-Lap) triggers apoptosis in a number of human breast and prostate cancer cell lines through a unique apoptotic pathway that is dependent upon NQO1, a two-electron reductase. Recently, our laboratory showed that beta-lap-exposed MCF-7 cells exhibited an early increase in intracellular cytosolic Ca(2+) from endoplasmic reticulum stores, and that BAPTA-AM (an intracellular Ca(2+) chelator) blocked these early increases and partially inhibited all aspects of beta-lap-induced apoptosis. We now show that exposure of NQO1-expressing breast cancer cells to beta-lap stimulates a unique proteolytic apoptotic pathway involving mu-calpain activation. No apparent activation of m-calpain was noted. Upon activation, mu-calpain translocated to the nucleus concomitant with specific nuclear proteolytic events. Apoptotic responses in beta-lap-exposed NQO1-expressing cells were significantly delayed and survival enhanced by exogenous over-expression of calpastatin, a natural inhibitor of mu- and m-calpains. Furthermore, purified mu-calpain cleaved PARP to a unique fragment (approximately 60 kDa), not previously reported for calpains. We provide evidence that beta-lap-induced, mu-calpain-stimulated apoptosis does not involve any known apoptotic caspases; the activated fragments of caspases were not observed after beta-lap exposures, nor were there any changes in the pro-enzyme forms as measured by Western blot analyses. The ability of beta-lap to trigger an apparently novel, p53-independent, calpain-mediated apoptotic cell death further support the development of this drug for improved breast cancer therapy.
...
PMID:Mu-calpain activation in beta-lapachone-mediated apoptosis. 1275 May 53


<< Previous 1 2 3 4 5 6 7 Next >>

---