Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In bicarbonate/CO2 buffer, Mn(II) and Fe(II) catalyze the oxidation of amino acids by H2O2 and the dismutation of H2O2. As the Mn(II)/Fe(II) ratio is increased, the yield of carbonyl compounds per mole of leucine oxidized is essentially constant, but the ratio of alpha-ketoisocaproate to isovaleraldehyde formed increases, and the fraction of H2O2 converted to O2 increases. In the absence of Fe(II), the rate of Mn(II)-catalyzed leucine oxidation is directly proportional to the H2O2, Mn(II), and amino acid concentrations and is proportional to the square of the HCO3- concentration. The rate of Mn(II)-catalyzed O2 production in the presence of 50 mM alanine or leucine is about 4-fold the rate observed in the absence of amino acids and accounts for about half of the H2O2 consumed; the other half of the H2O2 is consumed in the oxidation of the amino acids. In contrast, O2 production is increased nearly 18-fold by the presence of alpha-methylalanine and accounts for about 90% of the H2O2 consumed. The data are consistent with the view that H2O2 decomposition is an inner sphere (cage-like) process catalyzed by a Mn coordination complex of the composition Mn(II), amino acid, (HCO3-)2. Oxidation of the amino acid in this complex most likely proceeds by a free radical mechanism involving hydrogen abstraction from the alpha-carbon as a critical step. The results demonstrate that at physiological concentrations of HCO3- and CO2, Mn(II) is able to facilitate Fenton-type reactions.
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PMID:Manganese(II) catalyzes the bicarbonate-dependent oxidation of amino acids by hydrogen peroxide and the amino acid-facilitated dismutation of hydrogen peroxide. 229 94

Lactobionic acid, [4-beta-(galactosido)-D-gluconic acid] = LBA, is the major component of the Wisconsin organ transplantation preservant fluid and may suppress oxygen radical-induced tissue damage upon reperfusion by the control of FeII autoxidation. FeII and FeIII complexes of LBA and the related gluconic acid (GLC) have been studied herein by titrimetric, infrared, and electrochemical methods (CV; DPP). FeII(GLC) forms quickly at pH 7, but FeII(LBA) reacts in two steps, the second requiring 4 hr. The initial complex lacks coordination of the LBA carboxylate (C-1) and is bound by the "2,3,5" hydroxyl groups. The slow rearrangement forms a "1,2,3,6" chelate which FeII(LBA) shares in common with the donor set of the FeIII(LBA) complex. Titration data shows the removal of three protons from LBA through pH 5 and an additional proton from pH 6 to 9 which is indicative of the [FeIII(LBA)(OH)(H2O)]- formulation with LBA donating at the "1,2,3,6" positions. The more stable, second form of FeII(LBA) has been investigated in its oxidation mechanisms with H2O2 and O2 using selected trapping agents for HO. and ferryl intermediates. Eighty-six percent of the oxidation events of FeII(LBA)/H2O2 occurs in steps involving formation and reduction of freely diffusible HO.. These pathways are altered by the known HO. traps t-butanol, dmso, ethanol, and methanol in the manner predictable for beta-oxidizing radicals (from t-butanol or dmso) and alpha-reducing radicals (from ethanol and methanol). Fourteen percent of the FeII(LBA)/H2O2 reaction occurs via FeIVO intermediates not trapped by t-butanol or dmso, but intercepted by primary and secondary alcohols. The HO. generating pathways are responsible for a competitive LBA ligand oxidation at the C-2 position via HO., formed from FeII(LBA) and H2O2 within the original reaction cage. Competitive ligand oxidation at C-2 is absent for the FeII(LBA)/O2 autoxidation, indicative of a different redox mechanism. The FeII(LBA)/O2 reaction rate is first-order in each component and is insensitive to the presence of t-butanol as an HO. trap. These observations support a ferryl intermediate in the autoxidation pathway and the absence of HO. or free H2O2 during autoxidation. Although chelation of FeII by hard ligand donors such as edta4-, Cl-, or HPO4(2-) accelerate the rate of autoxidation of FeII, chelation of carboxylate, alkoxy, and hydroxyl donors of LBA does not accelerate autoxidation. The implications of these findings, and the absence of an inner-sphere coordination role of the 4-beta-(galactosido) functionality toward the action of LBA in organ preservant fluids, are discussed.
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PMID:Lactobionic and gluconic acid complexes of FeII and FeIII; control of oxidation pathways by an organ transplantation preservant. 843 86

Oxidation of NADH by decavanadate, a polymeric form vanadate with a cage-like structure, in presence of rat liver microsomes followed a biphasic pattern. An initial slow phase involved a small rate of oxygen uptake and reduction of 3 of the 10 vanadium atoms. This was followed by a second rapid phase in which the rates of NADH oxidation and oxygen uptake increased several-fold with a stoichiometry of NADH: O2 of 1:1. The burst of NADH oxidation and oxygen uptake which occurs in phosphate, but not in Tris buffer, was prevented by SOD, catalase, histidine, EDTA, MnCl2 and CuSO4, but not by the hydroxyl radical quenchers, ethanol, methanol, formate and mannitol. The burst reaction is of a novel type that requires the polymeric structure of decavanadate for reduction of vanadium which, in presence of traces of H2O2, provides a reactive intermediate that promotes transfer of electrons from NADH to oxygen.
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PMID:A novel phenomenon of burst of oxygen uptake during decavanadate-dependent oxidation of NADH. 851 Jun 71

Two separate, independent experiments were conducted to evaluate the effect of 60 Hz linearly polarized, sinusoidal, continuous-wave magnetic fields (MFs) on immune system performances in rats born and raised under these fields. Each experiment lasted for 6 weeks. A total of 96 animals, divided into groups of eight animals each, was exposed for 20 h/day to MFs of different intensities, i.e., sham (< 0.02 microT) and 2, 20, 200, and 2000 microT. Another group of animals, which was housed in a separate room, served as cage controls (CC). These animals were exposed to ambient MFs of < 0.02 microT. The following immune responses were evaluated in both experiments total T and B cells; CD4+ and CD8+ subpopulation and natural killer (NK) cell activity in splenic lymphocytes; hydrogen peroxide (H2O2), nitrous oxide (NO), and tumor necrosis factor (TNF) production by peritoneal macrophages. Our results show that a 6 week exposure to MFs induced a significant decrease in the number of CD5+, CD4+, and CD8+ populations. These changes were even more significant in rats that were exposed to fields of 2000 microT. A lower, although significant, decrease in the CD5+ population was also observed in animals that were exposed to fields of 200 microT. Linear regression analysis demonstrated a dose effect with MF intensity. B lymphocyte (Ig+ cell) populations also showed a 12% decrease (P < .05) in the groups that were exposed to fields of 20 and 200 microT. However, these results were not significant, and no relation with MF intensities could be demonstrated. In contrast, evaluation of splenic NK cell activity revealed a 50% increase (P < .05) in animals that were exposed to fields of 2000 microT. No significant results were obtained from the evaluation of TNF activity and NO secretion in peritoneal macrophages. Phorbol 12-myristate 13-acetate (PMA)-stimulated and net H2O2 productions for a minor subpopulation of peritoneal cells showed positive dose-response correlations by linear regression analysis. Taken together, our results suggest that an in vivo exposure of rats for 6 weeks to 60 Hz MFs can induce significant immunological perturbations on effector cells of both natural and adaptive immunity in a dose-dependent fashion.
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PMID:Differential modulation of natural and adaptive immunity in Fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields. 891 46

We have examined the reactions of peroxynitrite with short-chain aliphatic aldehydes to model the reaction of the peroxynitrite anion (ONOO-) with CO2. Aldehydes, like CO2, react rapidly with peroxynitrite and catalyze its decomposition. The pH dependence of the reaction is consistent with the addition of ONOO- (not ONOOH) to the carbonyl carbon atom of the free aldehyde forming a 1-hydroxyalkylperoxynitrite anion adduct (5), which structurally resembles the nitrosoperoxycarbonate adduct (1) formed from the reaction of ONOO- with CO2. Intermediate 5, or the secondary products derived from it, decays to give NO3- and regenerated aldehyde, with small but significant yields of H2O2, organic acids, and organic nitrates. In analogy with the peroxynitrite/CO2 system, it is suggested that 5 undergoes homolytic or heterolytic cleavage at the O-O bond, giving a caged radical pair [RCH(OH)O./ .NO2] (7) or intimate ion pair [RCH(OH)O -/+ NO2] (8). The radicals and ions in intermediates 7 and 8 can recombine within the solvent cage to form 1-hydroxyalkylnitrate [RCH(OH)ONO2] (6), which can then dissociate to give nitrate and regenerate the aldehyde. The aldehyde/ peroxynitrite adducts 5-8 mediate the oxidation of 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) but not the nitration of 4-hydroxyphenylacetate. The significance of these findings is discussed in relation to the mechanism(s) of the CO2-catalyzed isomerization of peroxynitrite to nitrate and biological nitrations involving peroxynitrite/CO2 adducts.
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PMID:Reactions of peroxynitrite with aldehydes as probes for the reactive intermediates responsible for biological nitration. 943 22

A computer-aided stochastic model of the radiolysis of liquid water has been developed. It is based on Monte Carlo simulation of charged-particle tracks, a random-flight method to simulate diffusion of species and the Debye-Smoluchowski theory of reactions between radicals. The model takes into account the formation of ionizations, excitations and subexcitation electrons at the physical stage. The corresponding initial yields at approximately 1 fs were found to be G(ion) = 4.37, G(exc) = 2.81 and G(e-sub) = 4.38. The energy spectrum of subexcitation electrons has been calculated. Autoionizations and dissociations of excited molecules, hole migration, electron thermalization, geminate recombination and the cage effect are considered at the physico-chemical stage. The mean thermalization distance of subexcitation electrons is 24.5 nm. The initial yields of e(aq)-, H+, OH, H, H2 and O are 4.89, 4.86, 5.96, 1.10, 0.15 and 0.15, respectively. The reactions between radicals and products as well as their diffusion are simulated at the chemical stage. The decay kinetics of the most important radicals is reported together with the time evolution of the most important reactions. The yields of the reactive radicals, e(aq)-, H+, OH, H and OH-, at 1 ps are 4.84, 4.85, 5.87, 1.09 and 0.0, respectively. The respective steady-state yields at 10 micros are 2.70, 3.58, 2.89, 1.17 and 0.79. The yields of molecular products, H2O2 and H2, are 0.73 and 0.47 at 10 micros. The concentration-dependent yields of e(aq)-, OH and H2O2 are calculated in three different aqueous solutions. The predictions of the model agree fairly well with experimental data.
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PMID:Computer-aided stochastic modeling of the radiolysis of liquid water. 949 85

Caprine alpha-2-macroglobulin (alpha2M) is a broad-spectrum, homotetrameric proteinase inhibitor that can maximally bind a single molecule of proteinase. Inhibition of proteinases by caprine alpha2M results from a series of conformational changes that are initiated by the proteinase and results in physical sequestration of the proteinase within the closed cage-like structure of conformationally altered alpha2M. In a previous study, uric acid-generated superoxide anion was identified as one of the physiologically relevant inactivators of alpha2M S.A. Khan, F.H. Khan [Free. Radic. Res. 34 (2001) 113]. We now demonstrate that hypochlorous acid (HOCl) and, to lesser extent, hydrogen peroxide (H2O2) destroy the antiproteolytic potential of caprine alpha2M. At physiologically attainable concentration, we found that HOCl significantly compromised functional integrity of the inhibitor. High concentrations of H2O2 also partially diminished proteinase inhibitory capacity of alpha2M by a mechanism not involving formation of hydroxyl radicals. For hydrogen peroxide, catalase completely protected alpha2M activity while the ability to protect the inhibitor from HOCl-induced inactivation was limited by availability of albumin. Structure function analysis demonstrated that oxidized caprine inhibitor, unlike its human counterpart, retained its tetrameric configuration as well as its characteristic ability to undergo major conformational change upon trypsinization. It is proposed that inhibition of alpha2M activity may be due to oxidation of essential residues of the inhibitor and/or structural rearrangement of the subunits.
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PMID:Oxidized caprine alpha-2-macroglobulin: damaged but not completely dysfunctional. 1537 18

Paradoxically, reactive oxygen species (ROS) can promote normal cellular proliferation and carcinogenesis, and can also induce apoptosis of tumor cells. In this report, we study the contribution of ROS to various cellular signals depending on the nature and the level of ROS produced. In nontransformed NIH 3T3 cells, ROS are at low levels and originate from NADPH oxidase. Hydrogen peroxide (H(2)O(2)), controlled by the glutathione system, is pivotal for the modulation of normal cell proliferation. In CT26 (colon) and Hepa 1-6 (liver) tumor cells, high levels of ROS, close to the threshold of cytotoxicity, are produced by mitochondria and H(2)O(2) is controlled by catalase. N-acetylcysteine, which decreases H(2)O(2) levels, inhibits mitogen-activated protein kinase and normal cell proliferation but increases tumor cell proliferation as H(2)O(2) concentration drops from the toxicity threshold. In contrast, antioxidant molecules, such as mimics of superoxide dismutase (SOD), increase H(2)O(2) levels through superoxide anion dismutation, as well as in vitro proliferation of normal cells, but kill tumor cells. CT26 tumors were implanted in mice and treated by oxaliplatin in association with one of the three SOD mimics manganese(III)tetrakis(4-benzoic acid) porphyrin, copper(II)(3,5-diisopropylsalicylate)2, or manganese dipyridoxyl diphosphate. After 1 month, the volumes of tumors were respectively 35%, 31%, and 63% smaller than with oxaliplatin alone (P < 0.001). Similar data were gained with Hepa 1-6 tumors. In conclusion, antioxidant molecules may have opposite effects on tumor growth. SOD mimics can act in synergy with cytotoxic drugs to treat colon and liver cancers.
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PMID:Controlling tumor growth by modulating endogenous production of reactive oxygen species. 1639 77

The equimolar reaction of 1-SH-2-R-1,2-closo-C2B10H10(R=Me, H, Ph) with KOH in ethanol produces the thiolate species [1-S-2-R-1,2-closo-C2B10H10]-. These react with iodine to give the disulfide bridged dicluster (1-S-2-R-1,2-closo-C2B10H10)2(R=H, Me, Ph) compounds as analytically pure, white and air-stable solids in high yield. Synthesis of monothioether bridged species is synthetically more difficult. In fact three procedures have been tested to obtain the thioether bridged dicluster compounds (2-R-1,2-closo-C2B10H10)2S (R=Me, H, Ph) but only (2-Me-1,2-closo-C2B10H10)2S was successfully synthesized and characterized. Attempts to produce mixed compounds (1-R-1,2-closo-C2B10H10)S(1-R'-1,2-closo-C2B10H10), R not=R', were unsuccessful. Deboronation reaction of this dicarboranylthioether lead, depending on the reaction conditions, to monoanionic [(2-Me-1,2-closo-C2B10H10)S(8-Me-7,8-nido-C2B9H10)]- or dianionic [(8-Me-7,8-nido-C2B9H10)2S]2- sulfur bridge anions. Deboronation of carboranyl disulfides gave the corresponding dianionic [(7-S-8-R-7,8-nido-C2B9H10)2]2-(R=H, Me, Ph) species. This reaction was very dependent, however, on the reaction conditions. With slight variation of the reaction conditions, splitting of the S-S bond leading to the thiolate species with retention of the closo cluster was also found. Carboranyl disulfides (1-S-2-R-1,2-closo-C2B10H10)2(R=H, Me, Ph) do not lead to thiosulfinates R-S(O)-S-R' by oxidation with H2O2 or I2 as organic disulfides do. This behaviour is attributed to the presence of the sulfur atom directly bonded to the carbon cluster that produces electronic transfer from the filled orbitals on the sulfur atom into the cage LUMO (largely located on the cage Cc-Cc bond). This causes a depletion of electron density on the sulfur, thence impairing sulfur oxidation, and facilitating S-S breaking. Crystal structures of monothioethers (2-Me-1,2-closo-C2B10H10)2S, [NMe4][(2-Me-1,2-closo-C2B10H10)S(8-Me-7,8-nido-C2B9H10)](the first example reported in the literature of a two cluster compound incorporating the closo C2B10 and the nido[C2B9]- moieties linked by a one member spacer) and disulfides (1-S-1,2-closo-C2B10H11)2, (1-S-2-Me-1,2-closo-C2B10H10)2, (1-S-2-Ph-1,2-closo-C2B10H10)2 are reported which support the behaviour of these species.
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PMID:Synthesis, reactivity and structural studies of carboranyl thioethers and disulfides. 1587 49

Evolution of an oxygenic atmosphere required primordial life to accommodate the toxicity associated with reactive oxygen species. We have characterized an archaeal antioxidant from the hyperthermophilic acidophile Sulfolobus solfataricus. The amino acid sequence of this approximately 22-kDa protein shares little sequence similarity with proteins with known function. However, the protein shares high sequence similarity with hypothetical proteins in other archaeal and bacterial genomes. Nine of these hypothetical proteins form a monophyletic cluster within the broad superfamily of ferritin-like diiron-carboxylate proteins. Higher order structural predictions and image reconstructions indicate that the S. solfataricus protein is structurally related to a class of DNA-binding protein from starved cells (Dps). The recombinant protein self assembles into a hollow dodecameric protein cage having tetrahedral symmetry (SsDps). The outer shell diameter is approximately 10 nm, and the interior diameter is approximately 5 nm. Dps proteins have been shown to protect nucleic acids by physically shielding DNA against oxidative damage and by consuming constituents involved in Fenton chemistry. In vitro, the assembled archaeal protein efficiently uses H2O2 to oxidize Fe(II) to Fe(III) and stores the oxide as a mineral core on the interior surface of the protein cage. The ssdps gene is up-regulated in S. solfataricus cultures grown in iron-depleted media and upon H2O2 stress, but is not induced by other stresses. SsDps-mediated reduction of hydrogen peroxide and possible DNA-binding capabilities of this archaeal Dps protein are mechanisms by which S. solfataricus mitigates oxidative damage.
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PMID:An archaeal antioxidant: characterization of a Dps-like protein from Sulfolobus solfataricus. 1602 30


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