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Biomedical subjects

A Guissani

Publications and source records attributed to A Guissani.

At least 19 recordsLinked to original sources
PubMed2001

Nasal polyp-derived superoxide anion: dose-dependent inhibition by nitric oxide and pathophysiological implications.

The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* inactivate reciprocally. The purpose of the present work was to evaluate the relationship between NO concentrations and nasal polyp production of O2-*. Polyp fragments from 24 patients were studied using histological examination and lucigenin-enhanced chemiluminescence (to assess O2-* production). The effect of various concentrations of exogenous NO on chemiluminescent signals was assessed. Basal and phorbol ester-stimulated O2-* production varied largely among patients, but both were highly related to eosinophilic infiltration. A slow releasing NO donor DETA NONOate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemiluminescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1.5 mM. The NO concentration in normal maxillary sinus was estimated about 10 ppm (i.e., 0.5 microM in aqueous phase) (Lundberg, et al. Nature Med 1995;1:370). Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM generate steady-state concentrations of NO of 0.5 microM and 2.5 microM, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20-40%) O2-* production from polyp eosinophils. Conversely, phagocytic-derived O2-* could contribute to decrease sinus NO concentration, further altering this natural local defense. Together, these events could participate in chronic inflammation and contribute to the pathophysiology of nasal polyps.

Acridines↗
PubMed2000

Indirect inhibition of mitochondrial dihydroorotate dehydrogenase activity by nitric oxide.

Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate to orotate in the pyrimidine biosynthesis pathway. It is functionally connected to the respiratory chain, delivering electrons to ubiquinone. We report here that inhibition of cytochrome c oxidase by nitric oxide (NO) indirectly inhibits DHODH activity. In digitonin-permeabilized cells, DEA/NO, a chemical NO donor, induced a dramatic decrease in DHO-dependent O(2) consumption. The inhibition was reversible and more pronounced at low O(2) concentration; it was correlated with a decrease in orotate synthesis. Since orotate is the precursor of all pyrimidine nucleotides, indirect inhibition of DHODH by NO may significantly contribute to NO-dependent cytotoxicity.

Animals↗
PubMed1999

Interactions of nitric oxide with hemoproteins: roles of nitric oxide in mitochondria.

Nitric oxide (NO) binds to metalloproteins, and particularly to hemoproteins in both ferrous and ferric states, with association and dissociation rate constants which cover many orders of magnitude. These chemical properties often provide clear explanations of enzymatic specificity. A basic and straightforward description of the versatility of NO chemistry and of the biological relevance of NO effects, as understood by biochemists as opposed to physiologists, is presented. NO effects on hemoglobin and soluble guanylate cyclase, two proteins directly involved in arterio-venous oxygen transport at quite different biological levels, are compared. NO and other N-oxides also play primary roles in several mitochondrial functions. Specific interactions with cytochrome c oxidase and cytochrome c are reviewed, and the effects of NO and other N-oxides on other iron-cluster-containing components of mitochondrial respiration are discussed.

Animals↗
PubMed1999

Postulated effects on water structure of some salts and protein denaturants as inferred from measurements of viscosity B coefficients: example of HbS polymerization.

Viscosity measurements have been performed on aqueous solutions of some solutes commonly used in biochemical practice, with a view to determine the B coefficients and their temperature dependence. The temperature dependence measured for some anions leads to a ranking of the latter in an order similar to that reported earlier from entropy data for their postulated efficiency in disrupting "water structure". The well known dependence of denaturing power of guanidinium salts on the anions is shown to be related to the temperature dependence of B coefficients. Urea and formamide do not appear from this criterion to be significantly "structure-breaking"; alkyl-substituted derivatives of urea and formamide, on the other hand, possess significant "structure-forming" properties. The results are of interest in relation to the known effects of salts and other solutes on the stability of protein structures in respect of denaturation, subunit dissociation or self assembly. A typical application is illustrated by studying the effect of two anions, namely nitrate and sulphate, on the polymerization of sickle cell hemoglobin (HbS). Nitrate, which is believed to disrupt water structure, acts as an inhibitor of HbS polymerization which, on the contrary, is favoured by sulphate, a postulated structure- former.

Biopolymers↗
PubMed1996

Protection by glutathione against the antiproliferative effects of nitric oxide. Dependence on kinetics of no release.

Pretreatment by L-buthionine sulfoximine (BSO), which inactivates gamma-glutamylcysteine synthetase and, therefore, inhibits glutathione (GSH) synthesis, greatly increased the sensitivity of tumor cells to the antiproliferative effects of several NO-donating compounds. The sensitization that resulted from depletion of cellular GSH pools was observed in tumor cells exhibiting different degrees of resistance to NO. In contrast, GSH depletion of tumor target cells did not affect their sensitivity to the cytostatic activity of activated macrophages and other NO-producing cells (EMT6 cells treated by interferon gamma and LPS). The kinetics for NO generation is a parameter that may differentiate NO-producing cells and short-lived NO donors. To study the relationship between the magnitude of NO fluxes and the increased toxicity on BSO-pretreated cells, two NO-releasing zwitterions derived from polyamines (NONOates) with different half-lives were selected. NO fluxes as a function of time were simulated, according to the donor half-life and initial concentration, and antiproliferative effects on control and BSO-treated cells were compared. GSH depletion increased the sensitivity of tumor cells in the case of the less stable NO donor only. We, thus, propose that intracellular GSH is specifically protective against high fluxes of NO.

Animals↗
PubMed1995

[Metalloproteins, cellular targets of nitric oxide: a concise review].

In this review we recall the main physical properties of nitric oxide. The irreversible reactions of NO with O2 and O2.-, which yield strongly oxydant and nitrosating, and therefore toxic, species, are described in kinetic terms. Nearly all metalloproteins are potential targets for NO, often detectable by EPR spectroscopy. The case of hemoglobin in vitro and within circulating erythrocytes, especially in pathophysiological cases, is particularly described. A few examples of hemoproteins activated or inhibited by NO are given. Results obtained with cellular systems responding to cytokines are summarized, together with the effects of NO synthesis on [FeS] clusters-containing proteins, on ribonucleotide reductase and on the proteins implicated in iron metabolism.

Animals↗
PubMed1994

[Nitric oxide: a biological effector. Detection using electron paramagnetic resonance].

Nitric oxide is synthesized in mammalian cells from L-arginine or from pharmaceutical drugs. It forms paramagnetic complexes with some metalloproteins, including hemoglobin. Induction of NOSi following LPS or cytokine activation of murine macrophages has various effects, such as inhibition of mitochondrial respiration and that of DNA biosynthesis through interaction of NO with specific metalloenzymes. Induction of NOSi in a generator cell such as macrophage gives the same metabolic effects in target cells. NO is also detected in pathological states such as septic shock, diabetes mellitus and allograft, where the inducible L-arginine-NO pathway plays an important role. Electron Paramagnetic Resonance spectroscopy enables to detect unambiguously such specific molecular targets for NO in mammalian whole cells and organelles.

Animals↗
PubMed1993

EPR characterization of molecular targets for NO in mammalian cells and organelles.

Nitric oxide is synthesized in mammalian cells from L-arginine or from pharmaceutical drugs. It forms paramagnetic complexes with some metalloproteins, inhibiting key enzymes in DNA synthesis, mitochondrial respiration, iron metabolism, etc. This article reviews how electron paramagnetic resonance spectroscopy helps to detect unambiguously such specific molecular targets for NO in mammalian whole cells and organelles. EPR has also been used for the detection of spin adducts of free NO by spin-trapping methods.

Animals↗
PubMed1991

Nitroglycerin metabolism by Phanerochaete chrysosporium: evidence for nitric oxide and nitrite formation.

We have demonstrated that a filamentous fungus Phanerochaete chrysosporium converts glyceryl trinitrate (GTN) into its di- and mononitrate derivatives concurrently with the formation of nitric oxide detected by electron paramagnetic resonance (EPR), and the formation of nitrite. The metabolisms of nitrite and nitrate by the fungus are evaluated and taken into account when considering GTN degradation. Lack of evidence for nitrate formation from GTN suggests that an esterase-type activity is not involved. Furthermore, the kinetics of appearance of the hemoprotein-NO and non-heme protein-NO (FeS-NO) complexes indicate that an enzymatic process producing NO directly from GTN may be involved concurrently with a glutathione transferase-like system.

Aerobiosis↗
PubMed1991

Nitric oxide, a biological effector. Electron paramagnetic resonance detection of nitrosyl-iron-protein complexes in whole cells.

Nitric oxide has been used for more than 20 years as an electron paramagnetic resonance probe of oxygen binding sites in oxygen-carriers and oxygen-metabolizing metalloenzymes. The high reactivity of NO with oxygen and the superoxide anion and its high affinity for metalloproteins led biochemists to consider NO as a highly toxic compound for a living cell. This assertion has recently been reconsidered following a number of discoveries of great significance: the finding of the activation of guanylate cyclase by NO, the recognition that NO is the precursor of nitrite and nitrate ions released in the activation of macrophages by endotoxin and cytokines, evidence that NO is an Endothelium-Derived Relaxing Factor, and the discovery of NO-biosynthesis from L-arginine, a pathway common in various biological cell-to-cell signalling processes. It is now admitted that NO plays a key bioregulatory role within mammalian cells, between cells of different types and in the host defence response. In the present review we have attempted to give a general picture of what is known of the chemical, physical, biochemical and biophysical properties of NO among the various nitrogen oxides. We have focussed on the structural information that can be obtained by electron paramagnetic resonance spectroscopy of nitrosyl-metalloprotein complexes. Finally we have shown how molecular targets of nitric oxide can be characterized, within whole cells, by electron paramagnetic resonance spectroscopy.

Animals↗
PubMed1990

A tetrameric iron superoxide dismutase from the eucaryote Tetrahymena pyriformis.

An iron-containing superoxide dismutase has been purified from the protozoan Tetrahymena pyriformis. It has a molecular weight of 85,000 and is composed of four subunits of equal size. The tetramer contains 2.5 g atoms of ferric iron. Visible absorption and electron spin resonance spectra closely resemble those of other iron-containing superoxide dismutases. The amino acid sequence of the iron superoxide dismutase was determined. Each subunit is made up of 196 residues, corresponding to a molecular weight of 22,711. Comparison of the primary structure with the known sequences of other iron-containing superoxide dismutases reveals a relatively low degree of identity (33-34%). However, a higher percentage identity is found with mammalian manganese-containing superoxide dismutases (41-42%). The amino acid sequence is discussed in consideration of residues that may distinguish iron from manganese or dimeric from tetrameric superoxide dismutases.

Amino Acid Sequence↗
PubMed1990

Kinetic studies of four types of nitroheterocyclic radicals by pulse radiolysis. Correlation of pharmacological properties to decay rates.

The chemical properties of the nitro radical of four types of nitroheterocyclic compounds, nitrofurans, 2-nitroimidazoles, 4(5)-nitroimidazoles, 5-nitroimidazoles, having radiosensitizing and cytotoxic properties, have been studied by pulse radiolysis. The acid-base equilibria involving the nitro radical, the imidazole ring and some residues on the heterocycle have been determined. The pH-dependence of the rate of the disproportionation reaction of the nitro radical have been extensively studied. While the nitro radical derived from nitrofurans, 4- and 5-nitroimidazoles had a second-order decay, those of the 2-nitroimidazoles were found to decay through simultaneous first-order and second-order processes. Intrinsic second-order rate constants of the decay of the radical species in its various acidic and basic forms, could be determined. The intrinsic rate constants that determine the overall decay rates in the physiologically important 6 to 7.5 pH-range could be related to the one-electron redox potential E7(1). The implication of such chemical properties to enzyme-catalyzed reduction processes and to the mechanisms of radiosensitization and cytotoxicity of nitroheterocyclic compounds are briefly discussed. Pharmacological properties such as in vitro radiosensitization efficiency or metabolic reduction rates could be related to two of the nitro radical intrinsic disproportionation rates.

Chemical Phenomena↗
PubMed1987

Radicals of nitroimidazole derivatives: pH dependence of rates of formation and decay related to acid-base equilibria.

Three analogous 5-nitroimidazoles, having radiosensitizing and cytotoxic properties, have been studied by pulse-radiolysis in N2O-saturated aqueous formate solutions. Rates of formation of the radicals ImNO2-. are found to have little pH dependence. Decay of the radicals always follows second-order kinetics. The observed rates of decay decrease by three to four orders of magnitude over the pH range 0-12. A pK at 2.3 has been observed kinetically for metronidazole. The pK assigned to the radical couple (ImH)NO2H./(ImH)-NO2-., or alternatively (ImH2+)-NO2-./(ImH)-NO2-., varies from 4.7 to 6.1, depending on the substituents on the imidazole ring. Intrinsic second-order rate constants for decay of the acidic form of the radical, of the anionic form and of the mixed reactions were determined. While the anionic radical reacts slowly with itself, both the acidic radical self-reaction and the mixed reaction proceed at fast rates. The implications of these chemical properties to the mechanisms of radiosensitization and cytotoxicity of the nitroaryl compounds are briefly discussed.

Acid-Base Equilibrium↗
PubMed1982

Radical scavenging and electron-transfer reactions in Polyporus versicolor laccase a pulse radiolysis study.

The interaction of the radicals OH, t-BuO, Eaq, CO2 and O2 with the copper oxidase, laccase, from Polyporus, has been studied by the pulse-radiolysis technique. Each of these radicals formed transient adducts with a broad absorption maximum around 310 nm. Analysis of the optical properties and of the very fast rates of formation of these compounds shows that each radical interacts with a limited number of sites on the polypeptide part of the protein amongst R-S-S-R, histidine and aromatic residues. Interaction with the carbonyl group of some of the peptides bonds is also possible. The few target sites are probably hit simultaneously and electron transfer between these sites may also occur. In all cases, ina subsequent step, intramolecular electron transfer from the polypeptide radical adducts leads to a partial reduction of the blue type-1 Cu2+ with rates varying between 10(3) adn 10(4) s-1. Further reduction of the type-1 CU2+ occurs through a slow intermolecular reaction between two laccase radical transient adducts. In the case of CO2 and O2, this slow reduction could alternatively be due to an intermolecular reaction between laccase and CO2 or O2. The oxidation radicals OH, Br2 and (SCN)2, which formed radical adducts with fully ascorbate-reduced laccase, did not induce any type-1 copper reoxidation.

Butanols↗
PubMed1978

[Quaternary structure and proteolysis of the polynucleotide phosphorylase from C. perfringens].

This report describes structural studies on purified polynucleotide phosphorylase from C. perfringens. A method is described for the purification of the enzyme which yields a product equivalent in activity to the native polynucleotide phosphorylase from E. coli. These studies revealed a molecular heterogeneity arising from successive stages of proteolysis, to which this enzyme is especially sensitive; unusally, the enzyme is obtained as a mixture of variable proportions of the native and proteolysed forms. We found in all cases a trimeric basic structure composed of the native (alpha) or proteolysed (lapha) or proteolysed (alpha', alpha") catalytic sub-units, However, the enzyme is rather easily dissociated into its sub-units, a phenomenon which seems to accompany proteolysis (Table). Under the action of either endogenous proteases or trypsin, two enzymatic forms are obtained: their quaternary structures seem analogous, but they differ in their catalytic properties from each other and from the initial enzyme. With some care at each step of purification, the polynucleotide phosphorylase of E. coli can be obtained exclusively in its native form. The greater susceptibility to proteolysis of the enzyme from C. perfrigens and the relationship between such degradation and quaternary structure seem to be at the origin of the peculiar behavior of this polynucleotide phosphorylase.

Chemical Fractionation↗
PubMed1976

Study on the structure-function relationship of polynucleotide phosphorylase: model of a proteolytic degraded polynucleotide phosphorylase.

It is already known that modification of E. coli polynucleotide phosphorylase by endogenous proteolysis induces drastic changes in both phosphorolysis and polymerisation reactions. The structural parameters of the proteolysed polynucleotide phosphorylase are described. The phosphorolysis of polynucleotide, which is quite progressive for the native enzyme, is shown to be only partially progressive for the degraded enzyme, owing to the loss of polymer attachment sites.

Escherichia coli↗