Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fluorescent indicator 4,5-diaminofluorescein (DAF-2) has been used to investigate the production of nitric oxide in the vicinity of intraparenchymal cerebral blood vessels. Slices of rat hippocampus 300-350 microm thick, were loaded with 5 microM DAF-2 diacetate. On exposure to light of 450-490 nm wavelength, point sources of fluorescence, 1.8+/-0.2 microm in diameter (mean+/-SEM), were observed in close apposition to the outer surface of the vascular smooth muscle wall of 10/15 arterioles. In fixed slices, resectioned and processed for nicotinamide adenine dinucleotide phosphate-dependent diaphorase, stained varicose fibres were also seen in close association with the smooth muscle wall of small arterioles. These findings suggest that tonic activity in perivascular nitrergic nerve fibres lying in close proximity to intraparenchymal microvessels may be a source of dilator tone within the parenchyma.
 ...
PMID:Fluorescent imaging of nitric oxide production in neuronal varicosities associated with intraparenchymal arterioles in rat hippocampal slices. 1104 74

Distribution of nitric oxide (NO)-producible neurons in the ventral nerve cord (VNC) of the earthworm was investigated by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry. Some neurons (20-30 microm in diameter) were intensely stained and were localized in areas between the 1st and 2nd lateral nerves in the ventral side of VNC. In contrast, no neurons including giant fibers were stained in the dorsal side. Endogenous NO production from VNC was visualized using a fluorescent dye, diaminofluorescein-2 diacethyl (DAF-2 DA). When VNC was incubated in a saline, a relative high level of NO was produced from the ventral side, especially from NADPH-d-positive neurons. Under high-K+ stimulation, NO was also detected in the giant fibers in the dorsal side of VNC. Our results suggest that the earthworm VNC constantly and relative highly produces NO as a neuromodulator, and that NO produced from the ventral side sometimes reaches and affects the giant fibers. In conclusion, we successfully visualized NO in the earthworm VNC by clarifying both the distribution of NO-producible neurons and the endogenous NO production.
 ...
PMID:Visualization of nitric oxide production in the earthworm ventral nerve cord. 1137 56

Photodynamic therapy (PDT) is a therapeutic modality used for the treatment of a variety of solid neoplasms. The principle of PDT is based on the selective uptake of a photosensitizing chemical in tumor tissue/cell followed by irradiation of tumors with visible light. The treatment results in a cascade of oxidative events causing cell death both in vitro and in vivo. Nitric oxide (NO) is a gaseous free radical, which is an important modulator of immune, endocrine and neuronal functions and plays an important role in the induction of apoptosis. Hypericin (HY) is a photosensitizing pigment from Hypericum perforatum that displays phototoxic effects in neoplastic cell lines. Our previous studies have shown HY induced apoptotic cell death in nasopharyngeal carcinoma and other tumor cells. To better understand the oxidative mechanism of apoptosis induced by HY, we hypothesized the role of NO in PDT, which is considered to be involved in a variety of physiological and pathological processes. We first demonstrated the presence of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) reactivity, a potential marker of NO synthesizing (NOS) enzyme both at light (LM) and electron microscopic (EM) level. Immunocytochemistry, using specific antibodies for NOS subtypes (constitutive, NOS I and inducible, NOS II), we observed that both NOS I and NOS II was present in all cell lines. The expression of both NOS I and NOS II was further verified using Western blot analysis as early as 15 min post PDT compared to that of drug-treated non-irradiated and light alone treated control cells. Our observation of NO production and distribution using the DAF-2 method is direct evidence of NO production in PDT-treated cells.
 ...
PMID:Nitric oxide mediated photo-induced cell death in human malignant cells. 1263 64

The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA) includes induction of chemopreventive mechanisms and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the "NO-specific" 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM donor, bioactivated by cellular esterase activity to release salicylates, NO(3)(-), and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery.
 ...
PMID:Quinone-induced activation of Keap1/Nrf2 signaling by aspirin prodrugs masquerading as nitric oxide. 2303 85