Disease relevance of Decr1

• Neurons containing NADPH-diaphorase are selectively resistant to quinolinate toxicity [1].
• Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo [2].
• The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection [2].
• A cell-free extract of E. coli transformed with the recombinant plasmid, in the presence of NADPH and Mg2+, efficiently converted [14C]farnesyl diphosphate into squalene [3].
• Activation of mitomycin C to an electrophile was equally supported by NADPH and NADH in EMT6 tumor cell sonicates under hypoxia [4].

Psychiatry related information on Decr1

• Expression of the transgene correlated with an attenuation of exploratory behavior and increased circling activity and coincided with enhanced neuronal NADPH diaphorase staining [5].
• Lesioning the C row of whiskers at day 1 (i.e. during the critical period of barrel formation) led to fused C barrels of diffuse NADPH diaphorase activity in the barrel fields [6].

High impact information on Decr1

• We show that pentose-phosphate-pathway generation of NADPH is critical for oocyte survival and that the target of this regulation is caspase-2, previously shown to be required for oocyte death in mice [7].
• These data suggest that exhaustion of oocyte nutrients, resulting in an inability to generate NADPH, may contribute to ooctye apoptosis [7].
• Electrons move from intracellular NADPH, across a chain comprising FAD (flavin adenine dinucleotide) and two haems, to reduce extracellular O2 to O2-. NADPH oxidase is electrogenic, generating electron current (I(e)) that is measurable under voltage-clamp conditions [8].
• NADPH-cytochrome P450 reductase has been purified to apparent homogeneity and demonstrated to supply reducing equivalents from NADPH to cytochrome P450 (refs 5-7) [9].
• Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro [10].

Chemical compound and disease context of Decr1

• This activation system was found a) to be only minimally cytotoxic by itself and b) to be able to mediate NADPH-dependent, dose-dependent toxicity, and transformation by activating the procarcinogens dimethylnitrosamine, 2-naphthylamine, 2-aminoanthracene, and aflatoxin B1 [11].
• Because endothelial NADPH oxidases produce ROS that can cause endothelial dysfunction, their inhibition by ascorbate may represent a new strategy for sepsis therapy [12].
• Since ethanol did not alter directly the P450-dependent activation or detoxification of parathion, and did not decrease NADPH levels, ethanol's antagonism of the acute toxicity of parathion may result from reduced availability of O2 [13].
• A nitroreductase enzyme has been isolated from Escherichia coli that has the unusual property of being equally capable of using either NADH or NADPH as a cofactor for the reduction of its substrates which include menadione as well as 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) [14].
• The greatest mitochondrial drug metabolism was achieved in the presence of NADPH as cofactor and hypoxia (MAC 16-specific activity, 3.67 +/- 0.58 nmol/30 min/mg; MAC 26 specific-activity, 3.87 +/- 0.71 nmol/30 min/mg) and was unaffected by the addition of the inhibitors dicoumarol and cytochrome P-450 reductase antiserum [15].

Biological context of Decr1

• The defect in triggering the respiratory burst in KCs was selective for the reduction of O2 by NADPH, in that reduction of O2 by endogenous arachidonate was readily demonstrate in response to zymosan [16].
• These kinetic changes, together with the measured intracellular concentration of NADPH, account quantitatively for the suppression of H2O2 release by deactivated macrophages, and are nearly the mirror image of the kinetic changes observed during macrophage activation [17].
• CYP2E1 deficiency neither prevented the development of NASH nor abrogated the increased microsomal NADPH-dependent lipid peroxidation, indicating the operation of a non-CYP2E1 peroxidase pathway [18].
• We propose that oxidative stress generated by pollen NADPH oxidases (signal 1) augments allergic airway inflammation induced by pollen antigen (signal 2) [19].
• Through an intricate mechanism, these enzymes transfer reducing equivalents from NADPH to bound FAD and subsequently to an active-site disulfide [20].

Anatomical context of Decr1

• Incubation of activated macrophages in MDF resulted in a marked increase in the Km of the oxidase for NADPH, from 0.06 mM to 0.67 mM [17].
• To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA) [21].
• The expression of NOS in astrocytes and microglial cells has been confirmed by immunocytochemical staining using an antibody to the inducible NOS of mouse macrophages and by histochemical staining for NADPH diaphorase activity [22].
• TAL(-/-) spermatozoa show loss of Deltapsi(m) and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH [23].
• Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages [24].

Associations of Decr1 with chemical compounds

• Detergent-permeabilized KCs generated no O2- in the presence of 1 mM NADPH, in striking contrast to all PC populations studied [16].
• TAL-H is a key enzyme of the nonoxidative pentose phosphate pathway (PPP) providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis [25].
• By a comparison of the 14CO2 produced from D-[1-14C]glucose and from D-[6-14C]glucose in the presence and absence of an electron acceptor (methylene blue), it was demonstrated that regeneration of NADP+ from NADPH was a rate-limiting step for the pentose phosphate pathway in the tumors [26].
• Sequence analysis revealed sequences compatible with binding domains for calcium/calmodulin, flavin mononucleotide, flavin adenine nucleotide and NADPH [27].
• When mouse MLg cells were treated with 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene in the presence of microsomal enzymes and NADPH after 5-iododeoxyuridine (IUDR) treatment, the induction rate of the endogenous C-type virus was increased fivefold to sixfold in comparison with the culture treated with IUDR only [28].

Physical interactions of Decr1

• Amino acid sequence analysis of tryptic peptides revealed significant similarity to the NADPH binding region of plant and animal NADPH-cytochrome P450 reductases and Bacillus megaterium cytochrome P450:NADPH-cytochrome P450 reductase [29].
• For the first time, the two putative components of the NADPH binding sites of fatty acid synthase were identified, thereby making it possible to assign the enoyl reductase and beta-ketoacyl reductase domains of the multifunctional fatty acid synthase [30].
• A mechanism of resistance to methotrexate. NADPH but not NADH stimulation of methotrexate binding to dihydrofolate reductase [31].
• Cytosolic malic enzyme activity is important for shuttles which transport NADPH equivalents from mitochondria to the cytosol [32].
• Comparison of the MLCR ternary complex with three structures reported previously for enzymes of the SDR family (all crystallized as complexes with NADH) reveals a pair of basic residues (Lys17 and Arg39) making strong electrostatic interactions with the 2'-phosphate group of NADPH [33].

Enzymatic interactions of Decr1

• Mammalian thioredoxin reductase (TrxR) catalyzes the reduction of oxidized thioredoxin in a NADPH-dependent manner, and contains a selenocysteine residue near the C-terminus [34].
• Glutathione reductase catalyzes the NADPH-dependent conversion of glutathione disulfide to glutathione and helps protect the lung from injury by reactive oxygen [35].
• CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals [36].

Regulatory relationships of Decr1

• Nevertheless, expression of Glut1 and HK1 promoted increased cytosolic NADH and NADPH levels relative to those of the control cells upon growth factor withdrawal, prevented activation of Bax, and promoted growth factor-independent survival [37].
• Expression of iNOS mRNA and macrophage NADPH diaphorase staining was inhibited by iNOS-specific antisense oligonucleotides [38].
• CONCLUSIONS: The protective role of IDPc and IDPm against gamma-ray-induced cellular damage can be attributed to elevated NADPH, reducing equivalents needed for recycling reduced glutathione in the cytosol and mitochondria [39].
• Our findings suggest that in mouse spermatozoa, the enhanced glutathione reductase and peroxidase activities induced by the spontaneous lipid peroxidation increases NADPH production from the pentose phosphate shunt, while in rabbit spermatozoa, NADPH production is much lower [40].
• The catalase-inhibited NADPH-dependent H(2)O(2) production (luminol assay) was lower in induced than noninduced microsomes [41].

Other interactions of Decr1

• The addition of NADPH to the TrxR2 crystals resulted in a color change, indicating reduction of the active-site disulfide and formation of a species presumed to be the flavin-thiolate charge transfer complex [20].
• Here, we show RANKL stimulation of BMM cells transiently increased the intracellular level of reactive oxygen species (ROS) through a signaling cascade involving TNF (tumor necrosis factor) receptor-associated factor (TRAF) 6, Rac1, and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) 1 [42].
• Therefore, these results indicate that ROS generated by a gp91-independent NADPH oxidase(s) are important for establishing an adequate inflammatory response to pneumococcal CSF infection [43].
• This function of GPX1 is associated with attenuating the prooxidant-induced oxidation of NADPH, NADH, lipid, and protein in various tissues [44].
• Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry [45].

Analytical, diagnostic and therapeutic context of Decr1

• Extracts from cells infected with the recombinant showed NADPH-dependent conversion of DHEA (Km, 13.6 microM) and pregnenolone (Km, 4.0 microM) to slower migrating forms on thin layer chromatography [46].
• Fluorescence quenching and reactive blue agarose chromatography studies revealed that it binds to NADPH with high affinity (K(dNADPH) = 66.9 +/- 2.3 nM) [47].
• Using the fluorescent probe dihydrorhodamine 123 (DHR), in vivo biochemical correction of the superoxide-generating NADPH oxidase system was detected by flow cytometry in 12.3% +/- 0.9% of phorbol myristate acetate-stimulated peripheral blood neutrophils at 4 weeks and 2.6% +/- 1.0% at 14 weeks after transplantation [48].
• Resident and LPS-elicited macrophages were stimulated with phorbol myristate acetate, disrupted by sonication, assayed for their content of NADPH, and fractionated by centrifugation [49].
• In support of these observations, we identified Nrf2-dependent genes encoding detoxification enzymes, glutathione-related proteins, antioxidant proteins, NADPH-producing enzymes, and anti-inflammatory genes using oligonucleotide microarrays [50].

References