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1.
Reactive oxygen species (ROS) production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. ROS are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Excessive NADPH oxidase activation and ROS overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation. NADPH oxidase is a complex enzyme composed of six proteins: gp91phox (renamed NOX2), p22phox, p47phox, p67phox, p40phox and Rac1/2. Inhibitors of this enzyme could be beneficial, by limiting ROS production and inappropriate inflammation. A few small non-peptide inhibitors of NADPH oxidase are currently used to inhibit ROS production, but they lack specificity as they inhibit NADPH oxidase homologues or other unrelated enzymes. Peptide inhibitors that target a specific sequence of NADPH oxidase components could be more specific than small molecules. Here we review peptide-based inhibitors, with particular focus on a molecule derived from gp91phox/NOX2 and p47phox, and discuss their possible use as specific phagocyte NADPH oxidase inhibitors. 相似文献
2.
Phagocytes utilize reactive oxygen species (ROS) to kill pathogenic microorganisms. The source of ROS is an enzymatic complex (the NADPH oxidase), comprising a membrane-associated heterodimer (flavocytochrome b (558)), consisting of subunits Nox2 and p22(phox), and four cytosolic components (p47(phox), p67(phox), p40(phox), and Rac). The primordial ROS (superoxide) is generated by the reduction of molecular oxygen by NADPH via redox centers located on Nox2. This process is activated by the translocation of the cytosolic components to the membrane and their assembly with Nox2. Membrane translocation is preceded by interactions among cytosolic components. A number of proteins structurally and functionally related to Nox2 have been discovered in many cells (the Nox family) and these have pleiotropic functions related to the production of ROS. An intense search is underway to design therapeutic means to modulate Nox-dependent overproduction of ROS, associated with diseases. Among drug candidates, a central position is held by synthetic peptides reflecting domains in oxidase components involved in NADPH oxidase assembly. Peptides, corresponding to domains in Nox2, p22(phox), p47(phox), and Rac, found to be oxidase activation inhibitory in vitro, are reviewed. Usually, peptides are inhibitory only when added preceding assembly of the complex. Although competition with intact components seems most likely, less obvious mechanisms are, sometimes, at work. The use of peptides as inhibitory drugs in vivo requires the development of methods to assure cell penetration, resistance to degradation, and avoidance of toxicity, and modest successes have been achieved. The greatest challenge remains the discovery of peptide inhibitors acting specifically on individual Nox isoforms. 相似文献
3.
Summary The incorporation of tyrosine-2-14C-15N into xanthocillin X (I) byPenicillium notatum Westling has been investigated showing that nitrogen of the isocyano groups originates from tyrosine, which is incorporated as C6-C2-N-unit.
1. Mitteilung:H. Achenbach undH. Grisebach, Z. Naturforsch.20b, 137 (1965). 相似文献
1. Mitteilung:H. Achenbach undH. Grisebach, Z. Naturforsch.20b, 137 (1965). 相似文献
4.
Summary Two possible mechanisms for oxidative phosphorylation are suggested, based on participation of quinones in the process.Both of them postulate the 1–4 addition of inorganic phosphate on a reactive quinone isomer (the quinone-methide II) without exchange of the quinone oxygen atoms. They also account for the P1-18OH2 exchange observed during oxidative phosphorylation.
Communication présentée au Symposium International de Chimie organique des Produits Naturels, Bruxelles (12–15 juin 1962). Résumé dans: Industrie Chimique Belge27, 558 (1962). 相似文献
Communication présentée au Symposium International de Chimie organique des Produits Naturels, Bruxelles (12–15 juin 1962). Résumé dans: Industrie Chimique Belge27, 558 (1962). 相似文献
5.
G. Galliani D. Monti G. Speranza P. Manitto 《Cellular and molecular life sciences : CMLS》1985,41(12):1559-1560
Summary Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O2
– with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochromec under the same conditions. 相似文献
6.
C. Fuganti D. Ghiringhelli P. Grasselli 《Cellular and molecular life sciences : CMLS》1978,34(3):297-298
Summary (1
R) [1-3H,2H1] 3-Phenylpropanol, the key intermediate in the synthesis of (4
R) [4-3H,2H1] D, L-homoserine and of the (4
S)-isomer, is obtained from (1
S) [1-2H1] 3-phenylpropanol and (1
RS) [1-3H] ethanol upon incubation with yeast alcohol dehydrogenase and NAD+; under similar conditions 2-phenylethanol undergoes very small exchange with [1-2H2] ethanol. 相似文献
7.
Summary Cu2+-complexes with different monodentate ligands PYR, e.g. pyridine, 2,4,6-collidine and imidazole, catalyse the oxidation ofo-phenylenediamine (H2B) to 3,5-dihydro-2-amino-3-iminophenazine (PHEN) by O2. Investigation of the electron paramagnetic resonance during reaction gives interesting details on the function of Cu2+ as a catalyser. The formation of mixed complexes (H2B)Cu2+(PYR) and its influence on the reaction rated[PHEN]/dt is demonstrated. In the ratedetermining reaction, Cu2+ is reduced to Cu+, which is reoxidized by O2. During reaction the ratio [Cu2+]/[Cu+] is determined by means of e.p.r. measurements. 相似文献
8.
M. Hüttemann V. Frank B. Kadenbach 《Cellular and molecular life sciences : CMLS》1999,55(11):1482-1490
A single cDNA of cytochrome c oxidase subunit VIa was characterised from liver, heart and the thermogenic organ of the partially
endotherm tuna fish. The amino acid sequence revealed high identity with subunit VIa from carp and trout, but low identity
to subunits VIaL (liver type) and VIaH (heart type) of mammalian cytochrome c oxidase. In reconstituted cytochrome c oxidase
from bovine heart, the H +/e− stoichiometry is decreased from 1.0 to 0.5 at high intraliposomal ATP/ADP ratios via exchange of bound ADP by ATP at the
matrix domain of the transmembraneous subunit VIaH. Reconstituted cytochrome c oxidase from bovine liver and kidney, containing
subunit VIaL, revealed H +/e− ratios below 0.5, independent of the ATP/ADP ratio. The results suggest the evolution of three types of subunit VIa. Subunits
VIaH and VIaL are postulated to participate in mammalian thermogenesis.
Received 3 May 1999; received after revision 10 June 1999; accepted 29 June 1999 相似文献
9.
Porcelli AM Ghelli A Mastrocola T Rugolo M 《Cellular and molecular life sciences : CMLS》1999,56(1-2):167-173
The Ca2+ ionophore ionomycin induced cytosolic [Ca2+]i elevation as well as strong activation of Cl− efflux in mouse mammary epithelial cell lines expressing wild-type or mutated (deletion of phenylalaline 508) cystic fibrosis
transmembrane conductance regulator (CFTR) or vector. Ionomycin-induced Cl− efflux was abolished by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, whereas both activators and inhibitors of phospholipase A2 had no effect, indicating the involvement of Ca2+-dependent Cl- channels. Stimulation of arachidonic acid release by ionomycin and phorbol ester was not significantly different between
wild-type or mutated cell lines, whereas vector-transfected cells exhibited a significant higher release, which was shown
to be due to larger amount of immunoreactive cytosolic phospholipase A2. These results indicate that phospholipase A2 activity of C127 cells was not influenced by the presence of wild-type or mutated CFTR.
Received 27 April 1999; received after revision 11 June 1999; accepted 23 July 1999 相似文献
10.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
11.
Summary After administration of various C2-compounds as well as leucine-2-14C toCatharanthus roseus shoots and glycine-2-14C toStrychnos nux vomica plants no specific incorporation into the non-tryptophan C9–10 moiety of indole alkaloids was observed. The results indicate that glycine-2-14C is transformed into serine and is incorporated via tryptophan into strychnine. 相似文献
12.
13.
T. Yamada K. Kageyama Y. Joh J. Konishi K. Ienaga 《Cellular and molecular life sciences : CMLS》1998,54(2):125-128
2′-O-Methylinosine (1) has been isolated for the first time and shown to be an intrinsic hypotensive principle. Its probable in vivo precursor,
2′-O-methyladenosine (3), showed stronger and even orally potent hypotensive activity. Resistance of the methyladenosine (3) against adenosine deaminase is thought to contribute to its long-lasting activity. The effect of both nucleosides (1 and 3) was not accompanied with any significant change in heart rate, which is often observed with adenosine.
Received 2 October 1997; accepted 28 October 1997 相似文献
14.
F. Buzzetti F. Eisenberg H. N. Grant W. Keller-Schierlein W. Voser H. Zähner 《Cellular and molecular life sciences : CMLS》1968,24(4):320-323
Summary A strain ofStreptomyces viridochromogenes produced a new crystalline antibiotic, Avilamycin, related to but not identical with Curamycin and Exfoliatin. Avilamycin, C63H94O35Cl2, gave on solvolytic degradation the following products: dichloroisoeverninic acid, 2-deoxy-d-rhamnose, 2,6-di-O-methylmannose, 4-O-methylfucose,l-lyxose and 3,5-diacetoxy--caprolactone. 相似文献
15.
The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid
cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 μM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase.
Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 μM of
either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder
was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of
polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug
treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity
against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.
Received 17 January 2002; received after revision 22 February 2002; accepted 22 February 2002 相似文献
16.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
17.
Summary DCP increases IAA destruction by bothLens andPhaseolus root breis. H2O2 inhibits catabolism byLens extracts but activates it whenPhaseolus is used, mainly when roots are cultivated in the dark and contain inhibitors of IAA destruction. DCP 1·10–3
M and H2O2 1·10–4 or 1·10–3 volume forLens and DCP 1·10–4
M and H2O2 1·10–3 volume forPhaseolus nullify auxin catabolism. 相似文献
18.
Summary The catalysis of H2O2 decomposition by Cu2+-complexes of RNA and DNA has been investigated. It is shown that both complexes decompose H2O2, but only the Cu2+-RNA-system shows peroxidative activity too, e.g. only in this case the nucleotide bases are degraded. Thermal denaturation of DNA also leads to a Cu2+-complex with peroxidative activity, the latter being dependent on the degree of denaturation.
V. Mitteilung:S. Petri, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 1778 (1966).
12. Mitteilung überMetallionen und H 2 O 2; 11. Mitteilung:H. Ch. Curtius, P. Anders, R. Zell, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 2256 (1966). 相似文献
V. Mitteilung:S. Petri, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 1778 (1966).
12. Mitteilung überMetallionen und H 2 O 2; 11. Mitteilung:H. Ch. Curtius, P. Anders, R. Zell, H. Sigel undH. Erlenmeyer, Helv. chim. Acta49, 2256 (1966). 相似文献
19.
W. Doepfner 《Cellular and molecular life sciences : CMLS》1966,22(8):527-528
Zusammenfassung Ein ACTH-Analogon:d-Ser1-Nle4-(Val-NH2)25--1-25-Corticotrophin wurde tierexperimentell sowie orientierend humanpharmakologisch untersucht. Das Pentacosapeptid (DW-75) zeigt auf Grund der Substitution von 3 Aminosäuren eine gegenüber Peptiden mit natürlicher Sequenz beachtlich erhöhte ACTH-Aktivität. 相似文献
20.
Zur Stereochemie der Propandioldehydrase-Reaktion 总被引:2,自引:0,他引:2
Summary Propanedioldehydrase is shown to convert both (+)-(S)-2-2H-propanediol,3, and (–)-(R)-1-2H2-propanediol,5, to specimens of deuterated propion-aldehyde, for which the (S)-configuration has been established. Thus, in the propanedioldehydrase reaction migration of hydrogen atoms from C–1 to C–2 always occurs with inversion of configuration. 相似文献