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Dunnigan-type familial partial lipodystrophy, also known as FPLD Type II and abbreviated as (FPLD2), is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes usually type 2, dyslipidemia, hypertension, and early endpoints of atherosclerosis. It can also result in hepatic steatosis. FPLD results from mutations in LMNA gene, which is the gene that encodes nuclear lamins A and C. Familial partial lipodystrophy Hegele, RA (December 2000). "Familial partial lipodystrophy: A monogenic form of the insulin resistance syndrome". Molecular Genetics and Metabolism. 71 (4): 539-44. doi:10.1006/mgme.2000.3092. PMID 11136544. Hegele, RA (September 2000). "Insulin resistance in human partial lipodystrophy". Current Atherosclerosis Reports. 2 (5): 397-404. ...
1. Akbarian S, Vinuela A, Kim JJ, Potkin SG, Bunney WE Jr., Jones EG. Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development. Arch Gen Psychiatry 1993;50:178-187. 2. Akbarian S, Vinuela A, Kim JJ, et al. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances in cortical development. Arch Gen Psychiatry 1993;50:169-177. 3. Akbarian S, Sucher NJ, Bradley D, et al. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 1996;16:19-30. 4. Arnold SE, Hyman BT, van Hoesen GW, Damasio AR. Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. Arch Gen Psychiatry 1991;48:625-632. 5. Borden LA, Bell SC, Ognyanov VI, et al. Glycine transport inhibitors as novel antipsychotic agents. Abstract, 35th Annual Meeting of the ACNP, ...
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disorder wherein symptoms resembling aspects of aging are manifested at a very early age. It is a genetic condition that occurs due to a de novo mutation in the LMNA gene encoding for the nuclear structural protein lamin A. The lamin family of proteins are thought to be involved in nuclear stability, chromatin structure and gene expression and this leads to heavy effects on the regulation and functionality of the cell machinery. The functional role of the large-conductance calcium-activated potassium channels (BKCa) is still unclear, but has been recently described a strong relationship with their membrane expression, progerin nuclear levels and the ageing process. In this study, we found that: i) the outward potassium membrane current amplitude and the fluorescence intensity of the BKCa channel probe showed higher values in human dermal fibroblast obtained from patients affected by HGPS if
We investigated emerin localisation in two different human cell lines that were deficient for synthesis of lamins A and C and two further cell lines that were deficient for lamin A synthesis and in which lamin C was mis-localised to the nucleolus. In each cell line either all or a majority of emerin was mis-localised to the ER. In addition, we used a dominant negative mutant of lamin B1 that selectively eliminates lamins A and C but not lamins B1 and B2 from the NE of HeLa cells. A consequence of eliminating lamins A and C from the NE was that emerin relocated from the NE to the ER, where it formed insoluble inclusions.. Our data suggest that lamin A has a central role in tethering both emerin and lamin C to the NE. The following evidence supports this model. Association of lamin C with the NE in two of the cell lines reported here is dependent upon the presence of lamin A, and in its absence lamin C organisation is disrupted such that most (SW 13) or all (Ramos) is mis-localised to the ...
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ortho-Quinones are produced in vivo through the oxidation of catecholic substrates by enzymes such as tyrosinase or by transition metal ions. Neuromelanin, a dark pigment present in the substantia nigra and locus coeruleus of the brain, is produced from dopamine (DA) and norepinephrine (NE) via an interaction with cysteine, but it also incorporates their alcoholic and acidic metabolites. In this study we examined the metabolic fate of ortho-quinones derived from the catecholamine metabolites, 3,4-dihydroxyphenylethanol (DOPE), 3,4-dihydroxyphenylethylene glycol (DOPEG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylmandelic acid (DOMA). The oxidation of catecholic substrates by mushroom tyrosinase was followed by UV-visible spectrophotometry. HPLC analysis after reduction with NaBH4 or ascorbic acid enabled measurement of the half-lives of ortho-quinones and the identification of their reaction products. Spectrophotometric examination showed that the ortho-quinones initially formed
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Nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B-cell colony-enhancing factor, is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide (NMN) from nicotinamide in the salvage pathway of NAD+ biosynthesis in mammals. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) converts NMN to NAD+. The expression of NAMPT is upregulated during activation of immune cells such as monocytes, macrophages, dendritic cells, T and B cells, as well as in amniotic epithelial cells upon stimulation with several inflammatory cytokines. NAMPT-specific inhibitor, FK866 was found to deplete intracellular NAD content, resulting in apoptotic cell death in many cancer cell lines without any DNA damaging effect. Recently, Nakahata K et al, demonstrated that NAMPT is required to modulate circadian gene expression and circadian oscillation of NAD+.. ...
An orally bioavailable methyl ester of fumaric acid and activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential neuroprotective, immunomodulating and radiosensitizing activities. Although the exact mechanism of action through which dimethyl fumarate exerts its neuroprotective and immunomodulatory effects have yet to be fully understood, upon oral administration, dimethyl fumarate is converted into its active metabolite monomethyl fumarate (MMF) and MMF binds to Nrf2. Subsequently, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase ...
The protocol I have seen and used calls for cryostat or sliding microtome/frozen sections of paraformaldehyde-fixed material. Mount sections on slides, I dont think I ever did free-floating sections. Dehydration and/or embedding kills the enzyme. Geoff Sharon Cooperman wrote: > Im going to try do some NADPH diaphorase on brain sections. I assume > you cant do the technique on formalin fixed, paraffin embedded > tissue, but I found a protocol in Current Protocols in Neuroscience > which says you can do the technique on tissue fixed in > paraformaldehyde which has been put on a slide prior to staining. Does > anyone know if this would work (if not should I use floating > sections?) and am I correct in assuming that paraffin embedded tissue > wont work? > > Thanks, > Sharon -- -- ********************************************** Geoff McAuliffe, Ph.D. Neuroscience and Cell Biology Robert Wood Johnson Medical School 675 Hoes Lane, Piscataway, NJ 08854 voice: (732)-235-4583; fax: -4029 ...
NDH shuttles electrons from NAD(P)H:plastoquinone, via FMN and iron-sulfur (Fe-S) centers, to quinones in the photosynthetic chain and possibly in a chloroplast respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be plastoquinone. Couples the redox reaction to proton translocation, and thus conserves the redox energy in a proton gradient.
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Two families with Emery-Dreifuss muscular dystrophy (EMD) have been studied with DNA markers mapping to Xq27.3----qter. No recombination was observed in 11 phase known meioses informative for the factor VIII gene (F8C) and eight phase known meioses informative for DXS15 (DX13), giving maximum lod scores of 3.50 and 2.50 respectively at a recombination fraction of zero. DXS52 (St14) showed one recombinant in 12 phase known meioses giving a maximum lod score of 2.62 at a recombination fraction of 0.07. These results map EMD to the distal end of the long arm of the X chromosome and are an important step in the development of tests for carrier detection and prenatal diagnosis.. ...
Zhou, Y.,Tan, C.K.,Ling, E.A. (1997). Distribution of NADPH-diaphorase and nitric oxide synthase-containing neurons in the intramural ganglia of guinea pig urinary bladder. Journal of Anatomy 190 (1) : 135-145. [email protected] Repository. https://doi.org/10.1017/S0021878296001549 ...
Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) also known as pre-B-cell colony-enhancing factor 1 (PBEF1) or visfatin is an enzyme that in humans is encoded by the NAMPT gene. This protein is the rate-limiting enzyme in the Nicotinamide adenine dinucleotide (NAD+) salvage pathway that converts nicotinamide to nicotinamide mononucleotide in mammals to enable NAD+ biosynthesis. NAMPT has also been reported to be a cytokine (PBEF) that promotes B cell maturation and inhibits neutrophil apoptosis. NAMPT is downregulated by an increase of miR-34a in obesity via a 3UTR functional binding site of NAMPT mRNA resulting in a reduction of NAD(+) and decreased SIRT1 activity. NAMPT catalyzes the following chemical reaction: nicotinamide + 5-phosphoribosyl-1-pyrophosphate (PRPP) ⇌ {\displaystyle \rightleftharpoons } nicotinamide mononucleotide (NMN) + pyrophosphate (PPi) Thus, the two substrates of this enzyme are nicotinamide and 5-phosphoribosyl-1-pyrophosphate (PRRP), whereas its two ...
Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. NAD(+)-dependent isocitrate dehydrogenases catalyze the allosterically regulated rate-limiting step of the tricarboxylic acid cycle. Each isozyme is a heterotetramer that is composed of two alpha subunits, one beta subunit, and one gamma subunit. The protein encoded by this gene is the gamma subunit of one isozyme of NAD(+)-dependent isocitrate dehydrogenase. This gene is a candidate gene for periventricular heterotopia. Several alternatively spliced transcript variants of this gene have been described, but only ...
This study has revealed that the integral inner nuclear membrane protein Src1 functions in gene regulation of subtelomeric genes and is embedded functionally in a network of factors, which participate in transcription-coupled mRNA export. Importantly, Src1 is associated with subtelomeric chromatin and thus can help to organize this region of the chromosomes. In previous studies, Src1 was shown to contain an intron with the possibility of alternative splicing (Davis et al., 2000; Rodríguez-Navarro et al., 2002). Our study revealed that both splice forms localize to the nuclear periphery and are integral inner nuclear membrane proteins (King et al., 2006). However, both proteins are not functionally equivalent. To the best of our knowledge, this is the first demonstration that two forms of a protein generated by alternative splicing in yeast have different functions.. The N domain of Src1 mediates nuclear targeting, and insertion into the nuclear membrane requires the first transmembrane span. ...
In higher plants, genes for subunits of respiratory chain complex I (NADH:ubiquinone oxidoreductase) have so far been identified solely in organellar genomes. At least nine subunits are encoded by the mitochondrial DNA and 11 homologues by the plastid DNA. One of the key components of complex I is the subunit binding the substrate NADH. The corresponding gene for the mitochondrial subunit has now been cloned and identified in the nuclear genome from potato (Solanum tuberosum). The mature protein consists of 457 amino acids and is preceded by a mitochondrial targeting sequence of 30 amino acids. The protein is evolutionarily related to the NADH-binding subunits of complex I from other eukaryotes and is well conserved in the structural domains predicted for binding the substrate NADH, the FMN and one iron-sulphur cluster. Expression examined in different potato tissues by Northern blot analysis shows the highest steady-state mRNA levels in flowers. Precursor proteins translated in vitro from the ...
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Product Details of P-Benzoquinone CAS 106-51-4 Benzoquinone p-Benzoquinone P-quinone PBQ Quinone, P-Benzoquinone CAS 106-51-4 Benzoquinone p-Benzoquinone P-quinone PBQ Quinone from China manufacturer on Hisupplier.com.
Soluble quinoprotein glucose dehydrogenase (EC 1.1.99.35, soluble glucose dehydrogenase, sGDH, glucose dehydrogenase (PQQ-dependent)) is an enzyme with systematic name D-glucose:acceptor oxidoreductase. This enzyme catalyses the following chemical reaction D-glucose + acceptor ⇌ {\displaystyle \rightleftharpoons } D-glucono-1,5-lactone + reduced acceptor This soluble periplasmic enzyme contains PQQ as prosthetic group, and is bound to a calcium ion. Electron acceptor is not known. Geiger, O.; Gorisch, H. (1986). "Crystalline quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus". Biochemistry. 25: 6043-6048. doi:10.1021/bi00368a031. Dokter, P.; Frank, J.; Duine, J.A. (1986). "Purification and characterization of quinoprotein glucose dehydrogenase from Acinetobacter calcoaceticus L.M.D. 79.41". Biochem. J. 239 (1): 163-167. PMC 1147254 . PMID 3800975. Cleton-Jansen, A.M.; Goosen, N.; Wenzel, T.J.; van de Putte, P. (1988). "Cloning of the gene encoding quinoprotein glucose ...
In enzymology, a 6,7-dihydropteridine reductase (EC 1.5.1.34) is an enzyme that catalyzes the chemical reaction a 5,6,7,8-tetrahydropteridine + NAD(P)+ ⇌ {\displaystyle \rightleftharpoons } a 6,7-dihydropteridine + NAD(P)H + H+ The 3 substrates of this enzyme are 5,6,7,8-tetrahydropteridine, NAD+, and NADP+, whereas its 4 products are 6,7-dihydropteridine, NADH, NADPH, and H+. This enzyme participates in folate biosynthesis. This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 5,6,7,8-tetrahydropteridine:NAD(P)+ oxidoreductase. Other names in common use include 6,7-dihydropteridine:NAD(P)H oxidoreductase, DHPR, NAD(P)H:6,7-dihydropteridine oxidoreductase, NADH-dihydropteridine reductase, NADPH-dihydropteridine reductase, NADPH-specific dihydropteridine reductase, dihydropteridine (reduced nicotinamide adenine dinucleotide), reductase, dihydropteridine reductase, ...
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ADP-ribosyl cyclases catalyze the transformation of nicotinamide adenine dinucleotide (NAD+) into the calcium-mobilizing nucleotide second messenger cyclic adenosine diphosphoribose (cADP-ribose) by adenine N1-cyclization onto the C-1 position of NAD+. The invertebrate Aplysia californica ADP-ribosyl cyclase is unusual among this family of enzymes by acting exclusively as a cyclase, whereas the other members, such as CD38 and CD157, also act as NAD+ glycohydrolases, following a partitioning kinetic mechanism. To explore the intramolecular cyclization reaction, the novel nicotinamide 2-fluoroadenine dinucleotide (2-fluoro-NAD+) was designed as a sterically very close analogue to the natural substrate NAD+, with only an electronic perturbation at the critical N1 position of the adenine base designed to impede the cyclization reaction. 2-Fluoro-NAD+ was synthesized in high yield via Lewis acid catalyzed activation of the phosphoromorpholidate derivative of 2-fluoroadenosine 5-monophosphate and coupling
Understanding the physical basis of enzyme catalysis is critical for deciphering the physiological function of enzymes, and for driving developments in contemporary areas of research, including de novo enzyme design for biotechnology and synthetic biology applications. The increasing knowledge of enzyme structure and mechanisms has led to a shift in the production of fine chemicals from traditional synthetic methods to more environmentally friendly and sustainable approaches. One of the most widely employed chemical reaction in industry for which biocatalytic routes are greatly explored is the asymmetric reduction of activated C=C bonds, which can be catalysed by members of the Old Yellow Enzyme family of ene-reductases. One such member is pentaerythritol tetranitrate reductase (PETNR), a flavin mononucleotide (FMN)-dependent enzyme that uses NADPH (and, less efficiently, NADH) as ancillary hydride donor. Previous kinetic studies of PETNR have inferred that quantum mechanical tunnelling and fast ...
The invention relates to benzoquinone ansamycin analogs useful for the treatment of cancer and other diseases or conditions characterized by undesired cellular proliferation or hyperproliferation. Therapies involving the administration of such benzoquinone ansamycin analogs, optionally in combination with an inhibitor of an HSP90 client protein, are useful to treat cancer and non-cancerous disease conditions.
TY - JOUR. T1 - Inactivation of neutrophil NADPH oxidase upon dilution and its prevention by cross-link and fusion of phox proteins. AU - Miyano, Kei. AU - Kitahara, Hiroki. AU - Ohmi, Shinobu. AU - Kakinuma, Katsuko. AU - Tamura, Minoru. PY - 2004/11/1. Y1 - 2004/11/1. N2 - Activation of the phagocyte NADPH oxidase involves assembly of p47 phox, p67 phox, Rac, and flavocytochrome b 558, and the activation can be triggered in a cell-free system with an anionic amphiphile. We find that the activated oxidase in a pure cell-free system was rapidly inactivated upon dilution. When the activated oxidase was treated with a chemical cross-linker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, the half-life of the oxidase in dilution was extended from 1 min to 4 h at 25°C. The cross-linked oxidase was resistant to inhibition by inactive flavin analogs, indicating that cross-linking prevents flavin exchange. When a fusion protein p67N-p47N plus RacQ61L was added, flavocytochrome b 558 became ...
Apr 13th, 9:00 AM Apr 13th, 10:00 AM Characterization of Recombinant PA1225: a Hypothetical NAD(P)H-Quinone Oxidoreductase from Pseudomonas aeruginosa Strain PAO1. Poster #18A. ...
TY - JOUR. T1 - Unexplored interactions between pyrroloquinoline quinone and β-nicotinamide adenine dinucleotide. AU - Jao, Hsi Jung. AU - Tsai, Pei Yi. AU - Wang, Chong Mou. PY - 2007/8/15. Y1 - 2007/8/15. N2 - The interactions between pyrroloquinoline quinone (PQQ) and β-nicotinamide adenine dinucleotide (NAD(H)) characterized by spectral and voltammetric means are reported in this paper. PQQ exists with six major acid-base derivatives in aqueous solutions; the derivative predominating at pH 3, denoted H2Q-, was characterized to be responsible for the electrochemical and photochemical activities of PQQ, such as for the photooxidation of NADH. In contrast, the derivatives predominating at pH , 5, such as HQ2- and Q3-, are responsible for the interaction with NAD+; the equilibrium constant was estimated to be ∼106. Although the basic derivatives are less active in emission compared to H2Q-, incorporating NAD+ can enhance their activity in this respect. The titrations of NAD+ with HQ2- and ...
Physiological quinones carrying isoprenoid side chains have been compared with homologues lacking the side chain, for their ability to carry electrons and protons from dithionite to ferricyanide, trapped in liposomes. Six differential observations were made: (1) Plastoquinone and ubiquinones, with a side chain of more than two isoprene units, are by far better mediators than their short-chain homologues. Also other benzoquinones lacking a long side chain are poor catalysts, except dimethyl-methylenedioxy-p-benzoquinone, a highly autooxidizable compound. Tocopherol is a good catalyst. (2) Vitamin K-1 and K-2 are poor mediators compared to vitamin K-3. (3) The reaction catalyzed by quinones carrying long isoprenoid side chains has an about three-fold higher activation energy, irrespective of the catalytic efficiency. (4) The reaction catalyzed by quinones lacking a long side chain follows pseudo first-order kinetics, while the reaction with quinones carrying a long side chain is of apparently higher order
Accumulating evidence suggests a role of oxidative stress in the pathophysiology of schizophrenia. The potent antioxidant sulforaphane (SFN) is an organosulfur compound derived from a glucosinolate precursor found in cruciferous vegetables such as broccoli, Brussels sprouts and cabbage. The protection afforded by SFN is thought to be mediated via activation of the NF-E2-related factor-2 (Nrf2) pathway and subsequent up-regulation of phase II detoxification enzymes and antioxidant proteins, through an enhancer sequence referred to as the electrophilic responsive element or antioxidant responsive element. Recently, we reported that SFN could attenuate behavioral abnormalities in mice after the NMDA receptor antagonist phencyclidine. Considering the potent antioxidant effects of SFN, we have a hypothesis that SFN would be a potential therapeutic drug for schizophrenia. The purpose of this study is to determine whether SFN-rich broccoli sprout extract have beneficial effects in patients with ...
Poly [ADP Ribose] Polymerase 2 (ADP Ribosyltransferase Diphtheria Toxin Like 2 or NAD(+) ADP Ribosyltransferase 2 or Poly[ADP Ribose] Synthase 2 or PARP2 or EC 2.4.2.30)-Pipeline Review, H1 2017. Summary. According to the recently published report Poly [ADP Ribose] Polymerase 2-Pipeline Review, H1 2017; Poly [ADP Ribose] Polymerase 2 (ADP Ribosyltransferase Diphtheria Toxin Like 2 or NAD(+) ADP Ribosyltransferase 2 or Poly[ADP Ribose] Synthase 2 or PARP2 or EC 2.4.2.30) pipeline Target constitutes close to 18 molecules. Out of which approximately 16 molecules are developed by companies and remaining by the universities/institutes. Poly [ADP Ribose] Polymerase 2 (ADP Ribosyltransferase Diphtheria Toxin Like 2 or NAD(+) ADP Ribosyltransferase 2 or Poly[ADP Ribose] Synthase 2 or PARP2 or EC 2.4.2.30)-Poly [ADP-ribose] polymerase 2 is an enzyme encoded by the PARP2 gene. It is involved in the base excision repair (BER) pathway, by catalyzing the poly (ADP-ribosylation) of a limited number of ...
Stage 14 Drosophila oocytes are arrested in first meiotic metaphase. A cell-free extract of these oocytes catalyzes apparent disassembly of purified Drosophila nuclei as well as of nuclear lamin polymers formed in vitro from isolated interphase lamins. Biochemically, the oocyte extract catalyzes lamin solubilization and phosphorylation as well as characteristic changes in one- and two-dimensional gel mobility. A previously unidentified soluble lamin isoform is easily seen after in vitro disassembly. This isoform is detectable but present only in very small quantities in vivo and is apparently derived specifically from one of the two interphase lamin isoforms. Cell-free nuclear lamina disassembly is ATP-dependent and addition of calcium to extracts blocks disassembly as judged both morphologically and biochemically. This system will allow enzymological characterization of cell-free lamina disassembly as well as molecular analysis of specific Drosophila mutants. ...
Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating endothelial cell proliferation and migration, primarily through the receptor tyrosine kinase VEGF receptor2 (Flk1/KDR). Reactive oxygen species (ROS) derived from NAD(P)H oxidase are critically important in many aspects of vascular cell regulation, and both the small GTPase Rac1 and gp91phox are critical components of the endothelial NAD(P)H oxidase complex. A role of NAD(P)H oxidase in VEGF-induced angiogenesis, however, has not been defined. In the present study, electron spin resonance spectroscopy is utilized to demonstrate that VEGF stimulates O2·− production, which is inhibited by the NAD(P)H oxidase inhibitor, diphenylene iodonium, as well as by overexpression of dominant-negative Rac1 (N17Rac1) and transfection of gp91phox antisense oligonucleotides in human umbilical vein endothelial cells (ECs). Antioxidants, including N-acetylcysteine (NAC), various NAD(P)H oxidase inhibitors, and N17Rac1 significantly ...
Phagocyte superoxide production by a multicomponent NADPH oxidase is important in host defense against microbial invasion. However inappropriate NADPH oxidase activation causes inflammation. Endothelial cells express NADPH oxidase and endothelial oxidative stress due to prolonged NADPH oxidase activation predisposes many diseases. Discovering the mechanism of NADPH oxidase activation is essential for developing novel treatment of these diseases. The p47(phox) is a key regulatory subunit of NADPH oxidase; however, due to the lack of full protein structural information, the mechanistic insight of p47(phox) phosphorylation in NADPH oxidase activation remains incomplete. Based on crystal structures of three functional domains, we generated a computational structural model of the full p47(phox) protein. Using a combination of in silico phosphorylation, molecular dynamics simulation and protein/protein docking, we discovered that the C-terminal tail of p47(phox) is critical for stabilizing its ...
Trifascicular block is a problem with the electrical conduction of the heart. It is diagnosed on an electrocardiogram (ECG/EKG) and has three features: prolongation of the PR interval (first degree AV block) right bundle branch block either left anterior fascicular block or left posterior fascicular block. Trifascicular block is important to diagnose because it is difficult to tell based on the surface ECG whether the prolonged PR interval is due to disease in the AV node or due to diffuse distal conduction system disease. In the former case, if the block at the AV node level becomes complete, the escape rhythm will originate from the bundle of His, which typically will generate heart rates in the 40s, allowing the individual to survive and complain of symptoms of fatigue or near-syncope to their physician. In the latter case, however, because the conduction system disease is diffuse in nature, the escape rhythm may be fascicular or ventricular, which may be at rates that are life-threateningly ...
The heterotetramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis. Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD. The homotetramer has NADPH-dependent quinone reductase activity. Both homotetramer and the heterotetramer have broad in vitro substrate specificity and can reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones.
Abstract Alanine triazole Mn-catalyzed 1,6-conjugate coupling/aromatization of para-quinone methides was developed with good to high yields under mild conditions. This protocol provided an efficient and practical route to the synthetically interesting functionalized methines and their analogues. Preliminary mechanistic experiments revealed 1,6-conjugate addition of nucleophiles to para-quinone methides (p-QMs). The manganese was acted as the Lewis acid.. ...
The lamin complement of nuclear matrix isolated from F9 embryonal carcinoma cells was studied during retinoic acid-induced differentiation in culture. Differentiation of the original cells into parietal endoderm-like cells was accompanied by the gradual appearance of lamins A and C while lamin B was present throughout all stages. Lamins were identified by their molecular masses, isoelectric points, recognition by a monoclonal antibody and a polyclonal antiserum, and by peptide mapping. The increase in the amounts of lamins A and C found in the matrix was due to de novo synthesis as no extranuclear pools of these lamins were detected in the undifferentiated cells. These results provide biochemical evidence that, as in amphibian embryogenesis, there are variations in nuclear lamina composition during mammalian development. ...
TY - JOUR. T1 - RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. AU - Singh, Anju. AU - Boldin-Adamsky, Swetlana. AU - Thimmulappa, Rajesh K.. AU - Rath, Srikanta K.. AU - Ashush, Hagit. AU - Coulter, Jonathan. AU - Blackford, Amanda. AU - Goodman, Steven N.. AU - Bunz, Fred. AU - Watson, Walter H.. AU - Gabrielson, Edward. AU - Feinstein, Elena. AU - Biswal, Shyam. PY - 2008/10/1. Y1 - 2008/10/1. N2 - Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of electrophile and xenobiotic detoxification enzymes and efflux proteins, which confer cytoprotection against oxidative stress and apoptosis in normal cells. Loss of function mutations in the Nrf2 inhibitor, Kelch-like ECH-associated protein (Keap1), results in constitutive activation of Nrf2 function in non-small cell lung cancer. In this study, ...
TY - JOUR. T1 - Effect of anions on the binding and oxidation of divalent manganese and iron in modified bacterial reaction centers. AU - Tang, Kai. AU - Williams, Jo Ann C.. AU - Allen, James P.. AU - Kálmán, László. PY - 2009/1/1. Y1 - 2009/1/1. N2 - The influence of different anions on the binding and oxidation of manganous and ferrous cations was studied in four mutants of bacterial reaction centers that can bind and oxidize these metal ions. Light-minus-dark difference optical and electron paramagnetic resonance spectroscopies were applied to monitor electron transfer from bound divalent metal ions to the photo-oxidized bacteriochlorophyll dimer in the presence of five different anions. At pH 7, bicarbonate was found to be the most effective for both manganese and iron binding, with dissociation constants around 1 μM in three of the mutants. The pH dependence of the dissociation constants for manganese revealed that only bicarbonate and acetate were able to facilitate the binding and ...
Glutathione S-transferases (GSTs) are a diverse family of phase II detoxification enzymes found in almost all organisms. Besides playing a major role in the detoxification of xenobiotic and toxic compounds, GSTs are also involved in the regulation of mitogen activated protein (MAP) kinase signal transduction by interaction with proteins in the pathway. An in vitro study was performed for Theta, Omega, Sigma GSTs and their interaction with MAP kinase p38b protein from the fruit fly Drosophila melanogaster Meigen (Diptera: Drosophilidae). The study included the effects of all five Omega class GSTs (DmGSTO1, DmGSTO2a, DmGSTO2b, DmGSTO3, DmGSTO4), all five Theta class GSTs (DmGSTT1, DmGSTT2, DmGSTT3a, DmGSTT3b, DmGSTT4), and one Sigma class glutathione transferase on the activity of Drosophila p38b, including the reciprocal effect of this kinase protein on glutathione transferase activity. It was found that DmGSTT2, DmGSTT3b, DmGSTO1, and DmGSTO3 activated p38b significantly. Substrate specificities ...
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A multi-biomarker approach was conducted in the scallop Chlamys farreri from three sites, denoted here as S1, S2, and S3, in Qingdao coastal areas of China in March, June, September and December 2014 to assess pollution from polycyclic aromatic hydrocarbons (PAHs) and to select appropriate biomarkers. A suite of biological responses of the gills and digestive glands of the scallops was assayed, including: (i) phase I detoxification enzymes of 7-ethoxyresorufin-O-deethylase (EROD), epoxide hydrolase (EH), and dihydrodiol dehydrogenase (DD) and phase II detoxification enzymes of glutathione-S-transferase (GST) and sulfotransferase (SULT); (ii) antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx); (iii) oxidative damage parameters: lipid peroxidation (LPO) expressed by malondialdehyde (MDA) contents, protein carbonylation (PC) and DNA damage (F value); and (iv) the metabolism-related genes of EH, DD, GST, SULT and SOD ...
The transcription factor NF-E2-related factor 2 (Nrf2) plays a critical role in the mammalian response to chemical and oxidative stress through induction of phase II detoxification enzymes and oxidative stress response proteins. We reported that Nrf2 expression was activated by deltamethrin (DM), a prototype of the widely used Parathyroid pesticides, in PC12 cells. However, no study has examined Nrf2 nuclear translocation and free radical production, two hallmarks of oxidative stress, in the mammalian brain in vivo. To this end, we examined translocation of Nrf2 and production of free radicals in rat brain exposed to DM. Indeed, DM initiated nuclear translocation of Nrf2 in a dose-dependent manner. Furthermore, Nrf2 translocation was accompanied by the expression of heme oxygenase-1 gene, an Nrf2-regulated gene linked to free radical production. Deltamethrin exposure promoted free radical formation in rat brain and reactive oxygen species generation in PC12 cells. Translocation of Nrf2 may be a ...
The NADPH oxidase generates microbicidal superoxide in phagocytes, and when defective it leads to chronic granulomatous disease (CGD). Oxidase specific proteins in the cytosol, p47phox and p67phox, as well as the small GTP binding protein p21rac are important for activation of superoxide production. Because the activity of this oxidase is normally tightly restricted to the phagocytic vacuole, and its temporal and spatial organisation might be regulated by cytoskeletal proteins, we examined the cytosolic phox proteins for interactions with cytoskeletal elements. p67phox copurified with a 57 kDa protein, identified as coronin, an actin binding protein that is important for movement and phagocytosis in Dictyostelium. Binding studies revealed that coronin attaches to the C-terminal half of p40phox, a binding partner of p67phox. The phox proteins and coronin had a similar distribution in the cell, and both accumulated around the phagocytic vacuole. PMA activation of adherent neutrophils resulted in a ...
PKC regulation of neutrophil NADPH oxidase was suggested 2 decades ago when it was shown to be stimulated by phorbol ester.30 It is possible that neutrophils or monocytes contribute to vascular oxidative stress. Thus, increased NADPH oxidase subunit expression in monocytes was demonstrated in diabetic patients and was partly normalized after lowering of plasma glucose.31 Vascular homologues of neutrophil NADPH oxidase are sources of a major part of ROS production in VSMC and endothelial cells during physiological and pathological conditions.29 However, this section focuses on regulation of vascular NAD(P)H oxidase.. In VSMC, angiotensin II stimulates vascular NAD(P)H oxidase.32 Angiotensin II is involved in the development of cardiovascular disease in people with and without diabetes, perhaps through mechanisms independent of hypertension.33 A very rapid angiotensin II-stimulated activation of NAD(P)H oxidase involving PKC may cause redox activation of c-Src, leading to a more sustained ...
MalaCards based summary : Chronic Granulomatous Disease, Autosomal, Due to Deficiency of Cyba, is also known as granulomatous disease, chronic, autosomal recessive, cytochrome b-negative, and has symptoms including hepatomegaly, splenomegaly and hepatic abscesses due to immunodeficiency. An important gene associated with Chronic Granulomatous Disease, Autosomal, Due to Deficiency of Cyba is CYBA (Cytochrome B-245 Alpha Chain). Affiliated tissues include neutrophil, testes and skin ...
in Talanta (2015). Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great ... [more ▼]. Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great therapeutic potential since this enzyme produces superoxide anion whose most of the other ROS derive. The measurement of NOX activity by cell-free systems is often used to test potential inhibitors of the enzyme. A major drawback of this technique is the possible interferences between inhibitors and the probe, ferricytochrome c, used to measure the activity. We designed the EquiNox2, a new pharmacological tool, to determine the direct interaction of potential inhibitors with equine phagocytic NOX and their effect on the enzyme activity or assembly. This method consists in ...