Biomedical subjects

J Torreilles

Publications and source records attributed to J Torreilles.

At least 19 recordsLinked to original sources

PubMed2001

Nitric oxide: one of the more conserved and widespread signaling molecules.

After the discovery of the vasodilatory functions of nitric oxide (NO), many signaling mechanisms involving NO were identified through experiments on mammals. NO activates soluble guanylyl cyclase to induce the formation of cGMP, stimulates ADP-ribosylation of GAPDH to alter cell energy production, and combines with superoxide to generate peroxynitrite. It then became clear that NO was a major messenger molecule in mammals, involved in the regulation of blood vessel dilatation, immune function and neurotransmission in the brain and peripheral nervous system. The wide spectrum of physiological effects of NO in mammals prompted researchers to look for the presence of NO in vertebrates and invertebrates. Parallel findings on the presence of NO signaling in vertebrates and invertebrates were observed, and then NO was found to be a signaling molecule widely spread throughout the metazoan kingdom and whose functions were highly conserved during evolution. These features were extended to the entire animal kingdom after the discovery of NOS activity in protozoa, yeasts and bacteria. Recently, the involvement of NO and NOS in plant disease resistance to infection was documented and many close similarities were detected between NO-dependent signaling mechanisms involved in plants and those identified in animals. All of these results indicated that NO is one of the earliest and most widespread signaling molecules in living organisms. This short review was aimed at marshalling recent information that led to this conclusion.

Animals↗

PubMed2001

In vitro production of peroxynitrite by haemocytes from marine bivalves: C-ELISA determination of 3-nitrotyrosine level in plasma proteins from Mytilus galloprovincialis and Crassostrea gigas.

BACKGROUND: Peroxynitrite is increasingly proposed as a contributor to defence system in marine bivalve. It can be formed by combination of superoxide and nitric oxide, and can react with tyrosine residues of proteins giving rise to 3-nitrotyrosine. RESULTS: The present article describes a competitive ELISA for the measurement of 3-nitrotyrosine contents of plasma proteins from marine bivalves by means of a monoclonal anti 3-nitrotyrosine antibody mouse IgG. CONCLUSIONS: This assay is sensitive enough to determine the amounts of 3-nitrotyrosine in plasma proteins from one animal only. Using the C-ELISA, we have shown that the phagocytosis of zymosan particles increased the 3-nitrotyrosine levels of plasma proteins from mussel M. galloprovincialis and oyster C. gigas 5.8 and 7.5 times respectively.

Animals↗

PubMed2001

Nitric oxide generation by hemocytes of the mussel Mytilus galloprovincialis.

The phagocytic activity of Mytilus galloprovincialis hemocytes is thought to be associated with NADPH-oxidase activity of the plasma membrane, thus producing superoxide anions. Few studies, however, have been devoted to nitric oxide release by these haemocytes. We investigated NO generation in M. galloprovincialis in order to understand its role in the defensive mechanisms of these organisms. The presence of NO-synthase-like enzymatic activity in protein homogenates from M. galloprovincialis hemocytes was revealed by the conversion of radiolabelled L-arginine to L-citrulline. We observed partial inhibition of the luminol-dependent chemiluminescence of stimulated M. galloprovincialis hemocytes by both NO-synthase inhibitors and superoxide dismutase, indicating that peroxynitrite (which results from the reaction between nitric oxide and superoxide anions) partially mediated this chemiluminescence. Furthermore, we confirmed the production of nitric oxide by M. galloprovincialis by highlighting the nitric oxide-synthase-dependence of the nitrate and nitrite production of stimulated hemocytes.

Animals↗

PubMed2001

[The contribution of invertebrate study to the biology of nitric oxide].

After the identification of nitric oxide (NO) with the endothelium derived-relaxing factor, many signaling mechanisms involving NO were identified through experiments on Mammals. NO activates soluble guanylyl cyclase leading to the formation of cGMP, stimulates the ADP-ribosylation of GAPDH, altering the cell energy production and combines with superoxide, generating cytotoxic peroxynitrite. NO was then progressively established as a major messenger molecule in Mammals. It is implied in the regulation of blood vessel dilatation, immune function, development and neurotransmission in brain and peripheral nervous system. Later, parallel findings were observed in Invertebrates and then, NO appeared as a signaling molecule widely spread throughout the animal kingdom and whose functions were highly conserved during evolution. The purpose of this short review is to highlight the contribution of Invertebrate studies to the knowledge of NO biology.

Animals↗

PubMed2000

In vitro production of superoxide and nitric oxide (as nitrite and nitrate) by Mytilus galloprovincialis haemocytes upon incubation with PMA or laminarin or during yeast phagocytosis.

The phagocytic process is one of the most important elements of the self-defence system in mammals as well as in molluscs. In mammalian phagocytes, superoxide participates in the innate defence system by combining with nitric oxide to generate peroxynitrite, a strong oxidant that possesses highly cytotoxic properties against bacteria. To evidence a role of nitric oxide in the self-defence system of the marine bivalve Mytilus galloprovincialis similar to the role observed in the mammalian defence system, we measured the generation of superoxide and nitrite/nitrate (the stable end products of nitric oxide) upon in vitro stimulation of M. galloprovincialis haemocytes with PMA, laminarin, LPS and by phagocytosis of Saccharomyces cerevisiae (yeast cells). We show that stimulation with PMA, laminarin and yeast cell phagocytosis promotes superoxide and nitrite/nitrate generation from M. galloprovincialis haemocytes. Inhibitors of NADPH oxidase and inhibitors of NO synthase decreased the nitrite/nitrate levels generated by M. galloprovincialis haemocytes showing that both NADPH oxidase and NO synthase pathways are involved in the self-defence system of M. galloprovincialis.

Animals↗

PubMed1999

Neurodegenerative disorders: the role of peroxynitrite.

Inflammatory reaction is thought to be an important contributor to neuronal damage in neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and the parkinsonism dementia complex of Guam. Among the toxic agents released in brain tissues by activated cells, we focus attention in this review on peroxynitrite, the product of the reaction between nitric oxide (NO) and superoxide. Peroxynitrite is a strong oxidizing and nitrating agent which can react with all classes of biomolecules. In the CNS it can be generated by microglial cells activated by pro-inflammatory cytokines or beta-amyloid peptide (beta-A) and by neurons in three different situations: hyperactivity of glutamate neurotransmission, mitochondrial dysfunction and depletion of L-arginine or tetrahydrobiopterin. The first two situations correspond to cellular responses to an initial neuronal injury and the peroxynitrite formed only exacerbates the inflammatory process, whereas in the third situation the peroxynitrite generated directly contributes to the initiation of the neurodegenerative process.

Alzheimer Disease↗

PubMed1998

[Cellular and molecular mechanisms of the stress response in marine bivalves].

To maintain their body integrity when aggressed, living organisms use a series of genetic and metabolic events constituting the stress response. Experiments carried out on man and superior vertebrates have shown that the stress response can be considered as a general adaptative syndrome. It constitutes one of the key elements of the defense system and can schematically be decomposed as an immediate response related to the release of preformed or formed de novo cytotoxic cell mediators and a delayed response with genomic interactions and induced protein synthesis. In invertebrates, experiments were essentially aimed at study of cytotoxic secreted agents during immediate response. However, the presence of cytokine like agents, NO-synthases and heat shock proteins were also found in molluscs, insects, annelids and echinoderrns. In marine bivalvia, informations on stress response are scarce and ftagmentary and, to the best of our knowledge, no coherent synthesis was carried out. The aim of the present work is to collect up to date results in this field and to carry out a comparative analysis of defense mechanisms known in vertebrates.

Acclimatization↗

PubMed1997

[Modulation of respiratory activity of renal macrophages in sea bass (Dicentrarchus labrax) by chronic exposure to sublethal concentration of ammonia].

Sea bass (Dicentrarchus labrax) were exposed for 71 days to three different ammonia concentrations corresponding to 0, 15 and 25% of the lethal threshold concentration causing the death of half a fish population in 96 hours. The study of the respiratory burst from sea bass renal macrophages showed that the luminol dependent chemiluminescence (CL) emitted following stimulation with mezerein is higher when fishes were previously exposed to ammonia. Therefore, it seemed that chronically exposure of fishes to sublethal concentrations of ammonia primed their renal macrophages to secrete higher amounts of oxygen activated species during respiratory burst, even several days after the transfer of fishes into a standard environment. The stimulated-macrophage CL was partially inhibited by sodium azide, superoxide dismutase and a nitric oxide-synthesis inhibitor, the N5-(-1-iminoethyl)-L-ornithine monochloride, showing that hydrogen peroxide, superoxide anions and nitric oxide were released by renal macrophages from sea bass during the respiratory burst. These reactive species could react together to generate peroxynitrite, a strong bactericidal agent.

Ammonia↗

PubMed1996

L-Arginine infusion after ischaemia-reperfusion of rat kidney enhances lipid peroxidation.

To assess the role of superoxide (O2-) and nitric oxide (NO) in ischaemic-reperfusion-induced acute renal failure, we investigated whether an activation of the L-arginine-NO pathway contributes to ischaemia-reperfusion-induced kidney membrane peroxidation by measurement of 4-hydroxynonenal (HNE) content in anaesthetized rats submitted to acute renal ischaemia. Following ischaemia-reperfusion injury, renal blood flow (RBF) was significantly reduced, while renal vascular resistance was significantly increased. Infusion of neither L-arginine nor D-arginine led to a recovery of RBF. L-Arginine, but not D-arginine, caused a significant increase in HNE accumulation in the ischaemic kidney. L-Arginine infusion enhanced the degree of lipid peroxidation afforded by ischaemia-reperfusion injury in the kidney suggesting that products of the endogenous L-arginine-NO pathway may react with O2- to initiate lipid peroxidation.

Aldehydes↗

PubMed1996

Potential role of the peroxidase-dependent metabolism of serotonin in lowering the polymorphonuclear leukocyte bactericidal function.

Serotonin (5-hydroxytryptamine, 5-HT) significantly and dose-dependently suppressed the luminol-enhanced chemiluminescence (CL) signal generated by polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate (PMA), but did not modify either lucigenin-enhanced CL or the reduction of superoxide dismutase-inhibitable cytochrome c. Moreover, stimulation of PMNs previously incubated with 5-HT resulted in a threefold increase in 5-HT equivalents bound to the proteins of PMN. The addition of catalase or sodium azide substantially reduced this binding. The present results suggest that 5-HT metabolism is mediated by H2O2 and myeloperoxidase (MPO) released by activated PMNs. Hence 5-HT could lower the bactericidal function of these cells by competition with hypochlorite formation from halides and MPO/H2O2.

Acridines↗

PubMed1996

[Reactive oxygen species and defense mechanisms in marine bivalves].

The main results published on the production of reactive oxygen intermediates by hemocytes and digestive glands of marine bivalves such as mussels, oysters or clams have been reviewed and discussed. Mussel and oyster hemocytes respond to appropriate stimuli with a burst of respiratory activity and the generation of reactive oxygen intermediates in a manner resembling the respiratory burst of mammalian phagocytes. However, interspecies differences in hemocytes-mediated antimicrobial defense mechanisms occur since clam hemocytes do not show any increase of reactive oxygen intermediate production upon similar stimulations. Hepatopancreatic gland of bivalves, as mammalian and fish liver produce reactive oxygen species during the one-electron reduction of xenobiotics, and mechanistic differences appear between bivalves and mammals. Thus, it appears that, in spite of some interspecies differences, the generation of cytotoxic reactive oxygen species is a general protective mechanism of most, if not all, animal species.

Animals↗

PubMed1995

Nitration of tyrosyl-residues from extra- and intracellular proteins in human whole blood.

We measured the amounts of tyrosine and 3-nitrotyrosine (NO2-tyrosine) in proteins of plasma and polymorphonuclear leukocytes (PMN) from human whole blood before and after activation with phorbol ester (PMA) or calcium ionophore (A 23187). In unstimulated blood, no significant nitration of tyrosine was detected into PMN proteins, but a NO2-tyrosine/tyrosine ratio of 0.7% was detected in plasma proteins. When blood was activated with PMA, the NO2-tyrosine/tyrosine ratio stayed at 0.7% in plasma proteins, but it increased to 1.4% in PMN proteins, indicating a peroxynitrite production within the cells. In blood activated with calcium ionophore, the NO2-tyrosine/tyrosine ratio was 1.2% in plasma proteins and 2.1% in PMN proteins. Incubation of blood with a NO-synthase inhibitor before stimulation inhibited such a protein tyrosine nitration. To ensure that NO2-tyrosine detected in intracellular proteins did not result from the enzymatic posttranslational tyrosylation of PMN proteins, the incorporation of 14C labeled tyrosine into PMN proteins after activation with PMA or A23187 was studied. The addition of a 10 fold excess of NO2-tyrosine did not modify the course of protein tyrosylation. Because tyrosine nitration is an irreversible reaction, NO2-tyrosine could be accumulated into proteins and could act as a cumulative index of peroxynitrite production.

Blood Proteins↗

PubMed1995

[Protection of oxidation of LDL by nitric oxide: implication in atherogenesis].

Superoxide (O2-) and nitric oxide (.NO) are free radicals which are known to react together leading to peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radical (OH degrees). .NO has been reported to have a dual effect on LDL oxidation (pro or antioxidant). In the present study we have investigated in vitro the action of exogenous .NO on human LDL oxidation promoted by oxygen, copper or (2,2'-azobis (2-aminodinopropane hydrochloride)(ABAP). .NO was given as NO donnor (sodium nitroprussiate or S-nitroso-L-glutathione) from 10 to 500 microM. Oxidation of LDL was measured by monitoring continuously conjugated diene formation at 234 nm. Exogenous .NO inhibited in a dose dependent manner the progress of spontaneous LDL oxidation. Copper--or ABAP--induced oxidation were characterized by lag, propagation and decomposition phases. Exogenous .NO decreased the propagation rate of LDL oxidation and the level of maximal diene production. These effects are different of these of alpha-tocopherol, a chain-breaking antioxidant. In our experimental conditions, .NO exhibited antioxidant activities. In vivo, the continuous release of endogenous .NO could protect LDL from cell-induced oxidation.

Amides↗

PubMed1995

[Does nitric oxide stress exist?].

Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism. This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment. Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress. Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion. However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation. Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production. inhibition of ribonucleotide reductase: extensive inhibition of this key enzyme in DNA synthesis in the presence of large amounts of NO could lead to important antiproliferative effects; inhibition of cytochrome P450-dependent metabolism: in Kupffer cells and hepatocytes, LPS-induced overproduction of NO has been shown to inhibit cytochrome P450-dependent metabolism and to mediate the suppression of hepatic metabolism. Moreover, NO synthetized in the peripheral nervous system is known to mediate nonadrenergic noncholinergic (NANC) neurotransmission. Overstimulation of NO synthases might therefore contribute to pathophysiological states such as: gastrointestinal motility, reflux oesophagitis, asthma, adult respiratory distress syndrome (ARDS) and chronic pulmonary artery hypertension. To these NO-mediated biological functions, one could add the biological effects of NO-derivatives such as N-nitrosocompounds, which act as carcinogenic agents, or C-nitrosocompound which were recently used as "zinc-ejecting" agents to inhibit HIV-1 infectivity of human T-lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Free Radicals↗

PubMed1995

[Nitric oxide and lipid peroxidation].

Nitric oxide (NO) is a free radical produced enzymatically in biological systems from the guanidino group of L-arginine. Its large spectrum of biological effects is achieved through chemical interactions with different targets including oxygen (O2), superoxide (O2o-) and other oxygen reactive species (ROS), transition metals and thiols. Superoxide anions and other ROS have been reported to react with NO to produce peroxynitrite anions that can decompose to form nitrogen dioxide (NO2) and hydroxyl radial (OHo). Thus, NO has been reported to have a dual effect on lipid peroxidation (prooxidant via the peroxynitrite or antioxydant via the chelation of ROS). In the present study we have investigated in different models the in vitro and in vivo action of NO on lipid peroxidation. Copper-induced LDL oxidation were used as an in vitro model. Human LDL (100 micrograms ApoB/ml) were incubated in oxygene-saturated PBS buffer in presence or absence of Cu2+ (2.5 microM) with increasing concentrations of NO donnors (sodium nitroprussiate or nitroso-glutathione). LDL oxidation was monitored continuously for conjugated diene formation (234 nm) and 4-hydroxynonenal (HNE) accumulation. Exogenous NO prevents in a dose dependent manner the progress of copper-induced oxidation. Ischaemia-reperfusion injury (I/R), characterized by an overproduction of ROS, is used as an in vivo model. Anaesthetized rats were submitted to 1 hour renal ischaemia following by 2 hours of reperfusion. Sham-operated rats (SOP) were used as control. Lipid peroxidation was evaluated by measuring the HNE accumulated in rats kidneys in presence or absence of L-arginine or D-arginine infusion. L-arginine, but not D-arginine, enhances HNE accumulation in I/R but not in SOP (< 0.050 pmol/g tissue in SOP versus 0.6 nmol/g tissue in I/R), showing that, in this experimental conditions, NO produced from L-arginine, enhances the toxicity of ROS. This study shows that the pro- or antioxydant effects of NO are different in vivo and in vitro and could be driven by environmental conditions such as pH, relative concentrations of NO and ROS, ferryl species.

Animals↗

PubMed1995

[Casein-derived peptides can promote human LDL oxidation by a peroxidase-dependent and metal-independent process].

The results of the present study revealed that peptides derived from bovine casein hydrolysates can promote peroxidase-dependent oxidation of human low-density lipoproteins (LDL). The reaction was independent of the free metal ions but required casein-derived peptides with tryosyl-residues, implying that the tyrosyl radical is a diffusible catalyst that conveys oxidizing potential from the active site of the heme enzyme to LDL lipids. This mechanism is independent of the peroxidase used to oxidize tyrosyl residues since myeloperoxidase and horseradish peroxidase mediate a similar LDL peroxidating process. Vitamin E, ascorbic acid, butylated hydroxytoluene and reduced glutathione delayed LDL oxidation and were consumed during the reaction, they transfered hydrogen to repair tyrosine.

Antioxidants↗

PubMed1995

[Free radicals and natural or synthetic chemiluminescent systems].

Studies of chemical mechanisms involved in the reactivity of natural or synthetic chimioluminescent compounds show that chimioluminescent phenomena result always from redox reactions associated with energy transfers and often with electron transfers. Therefore, analytical methods based on chimioluminescence are very well adapted to detect and evaluate the free radicals: reactive oxygen species, nitric oxide and non oxygenated radicals, which are generated in biological systems.

Animals↗

PubMed1994

[Measurement of nitric oxide and biological systems].

Interest in NO measurement strongly increased with the discovery that NO is endogenously produced by living tissues. This review describes the major techniques for quantification of NO and derivatives in biological models.

Electron Spin Resonance Spectroscopy↗