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C Cambon

Publications and source records attributed to C Cambon.

At least 19 recordsLinked to original sources
PubMed2001

Dopamine induces ERK activation in renal epithelial cells through H2O2 produced by monoamine oxidase.

BACKGROUND: The rat renal proximal tubule cells contain a large amount of monoamine oxidase, which catalyzes the oxidative deamination of catecholamines such as dopamine (DA). The aim of this study is to investigate the potential role of hydrogen peroxide (H2O2) produced by monoamine oxidase (MAO) isoform on regulation of cell signaling and function. METHODS: Primary rat proximal tubular cells, which contain almost exclusively MAO-A, and human embryonic kidney 293 (HEK 293) cells stably transfected with human MAO-B cDNA were treated with DA or tyramine in the presence or the absence of some inhibitors. Then, Shc protein tyrosine phosphorylation and extracellular-regulated kinase (ERK) activation were evaluated by immunoprecipitation/immunoblot analysis and cell proliferation by [3H]thymidine incorporation or cell counting. RESULTS: In rat proximal tubule cells, DA induced tyrosine phosphorylation of Shc, ERK activation, and a significant increase in DNA synthesis. The involvement of MAO-dependent H2O2 generation induced by DA (5 micromol/L) was supported by the demonstration that the DA effects were (1) fully prevented by cell pretreatment with the MAO inhibitor pargyline, the antioxydant N-acetylcysteine (NAC), and the DA uptake inhibitor GBR 12909; (2) not abrogated by the D1 and D2 receptor antagonists; (3) observed in HEK 293 MAO-B cells but not in HEK 293 wild-type cells, which do not express MAO; and (4) similar to those induced by another MAO substrate, tyramine. CONCLUSIONS: Taken together, these results show that in addition to the effects related to receptor stimulation, DA, and probably the other catecholamines, may induce some of its effects through the MAO-dependent H2O2 production.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Hydrogen peroxide generation by monoamine oxidases in rat white adipocytes: role on cAMP production.

In rat, white adipocytes monoamine oxidases (EC 1.4.3.4.) generate hydrogen peroxide (H(2)O(2)). Recent studies suggested that, in addition to its toxic features, H(2)O(2) may behave as a cell second messenger. In the present study, using fluorimetric and chemiluminescence (CL) assays, we showed that tyramine degradation by monoamine oxidases in intact adipocytes resulted in the concentration-dependent generation of H(2)O(2). In addition, we found that, in the presence of low tyramine concentrations, forskolin-dependent cAMP production was significantly increased as compared to that of the control and this increase was prevented by the monoamine oxidase inhibitor pargyline or by the H(2)O(2) trapping system homovanillic acid-peroxidase. Finally, we demonstrated that tyramine degradation by monoamine oxidases increased the ability of isoproterenol to induce cell lipolysis. Taken together, these data suggest that H(2)O(2) produced during substrate degradation by monoamine oxidases may participate in the regulation of adipocyte metabolism.

Adipocytes↗
PubMed2000

Monoamine oxidase B induces ERK-dependent cell mitogenesis by hydrogen peroxide generation.

The mitochondrial enzyme monoamine oxidase (MAO) A and B catalyze the oxidative deamination of various endogenous and exogenous biogenic amines. In the present study, we used human embryonic kidney 293 (HEK 293) cells stably transfected with human MAO-B cDNA to investigate the potential role of hydrogen peroxide (H(2)O(2)) produced by MAO-B isoform as an intracellular messenger involved in regulation of cell signaling and function. The MAO substrate tyramine induced tyrosine phosphorylation of Shc, ERK activation, and an increase in DNA synthesis in HEK 293 expressing MAO-B, but not in wild type HEK 293 cells, which do not express MAO. Tyramine effects were fully prevented by cell pretreatment with the MAO inhibitor pargyline or the antioxidant N-acetylcysteine. These results show that MAO-B induces MAPK/ERK activation and cell mitogenesis through H(2)O(2) production.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Reactive oxygen species production by monoamine oxidases in intact cells.

Monoamine oxidase (MAO) A and B are mitochondrial enzymes involved in the oxidative deamination of endogenous and exogenous amines. At present, the production of H2O2 by MAO in intact cells and its functional consequences in cell function have not been extensively investigated. The aim of this study was to define whether, in intact cells, the metabolism of small amounts of MAO substrates was able to induce a detectable H2O2 production. Hydrogen peroxide production was measured using a luminol-amplified chemiluminescence assay in three cell types, rat mesangial cells, rabbit proximal tubule cells and Hep-G2 cells, containing different MAO A/MAO B ratios. Our results showed that cell incubation with tyramine (50 micromol/l) led to a time-dependent H2O2 generation which was fully inhibited by MAO A (clorgyline and RO 41-1049) and MAO B (selegiline and RO 19-6327) inhibitors. The extent of inhibition of H2O2 production by selective inhibitors was in agreement with the amount of MAO isoforms expressed in each cell type, as determined by Western blot analysis and enzyme assay. Altogether, these findings show that, in a normal cell environment, MAO can be a source of reactive oxygen species which could have a functional impact on cell functions. In addition, we propose the luminol-amplified chemiluminescence assay as a rapid and sensitive procedure to characterize the monoamine oxidase isoforms and their regulation in intact cells.

Animals↗
PubMed1998

IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production.

Here we analysed the involvement of tyrosine phosphorylation in the regulation of the initial molecular events induced by IL-13 to modulate TPA-triggered reactive oxygen intermediates (ROI) production. Our data indicate that treatment of monocytes with a protein tyrosine kinase inhibitor (herbimycin A) prevents IL-13-induced cAMP accumulation and subsequent ROI inhibition. We have previously demonstrated that cAMP accumulation depends on inositol phosphates hydrolysis (InsPs) and intracellular Ca2+ mobilisation. The inhibition of InsPs and intracellular Ca2+ release by herbimycin A suggests a primary role of tyrosine kinases upstream PLC activation. We further specify that IL-13 stimulates PLC-gamma 1 and IRS-2 tyrosine phosphorylation in human monocytes. We demonstrate for the first time that IL-13 induces the association of IRS-2 with PLC-gamma 1. We proposed here that PLC-gamma 1 is a new candidate recruited by IRS-2.

Benzoquinones↗
PubMed1998

Immunocytochemical characterization of lung macrophage surface phenotypes and expression of cytokines in acute experimental silicosis in mice.

The expression of the surface phenotypical profile and the cytokines TNF-alpha and IL-1beta from murine lung macrophages was studied in parenchymal lung tissue and bronchoalveolar fluid of mice, over a 2-week period, following a single intratracheal instillation of silica. The acute inflammatory reaction, confirmed by a significant augmentation of four times the control values of the number of macrophages recovered by lavage from experimental animals, was followed by organized granulomas in the interstitium. The immunohistochemical analysis of lung tissue sections after silica instillation demonstrated the increased alveolar and interstitial tissue expression of all surface antigens and cytokines studied, mainly Mac-1, F4/80 antigens, TNF-alpha and IL-1beta, which were occasionally observed in normal uninjected and saline-treated mice. These findings show that, after silica instillation, the expression of surface phenotypical markers of lung macrophages increased, and this change was concomitantly associated with an increased expression of the cytokines TNF-alpha and IL-1beta. These changes support the conclusion that an influx of the newly recruited and activated macrophage population, with a different phenotype, is induced by treatment during inflammation. The populational changes involve difference in functional activity and enhance TNF-alpha and IL-1beta expression. These cytokines, produced in the silicosis-induced inflammatory process, are associated with the development of fibrosis and may contribute to disease severity.

Acute Disease↗
PubMed1996

Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica.

Exposure to mineral dusts such as silica has been associated with progressive pulmonary inflammation and fibrosis. There is evidence that the release of reactive oxygen intermediates (ROI) and cytokines by alveolar macrophages (AM) is involved in lung injury associated with silica exposure. However, the chronology and relationship between these two mediators are poorly understood. In this study, an animal model of silicosis has been used, allowing simultaneous follow-up of lung histopathologic state, AM TNF-alpha production at the protein (biologic assay) and mRNA (reverse transcriptase-PCR) levels, and the release of ROI (luminol-dependent chemiluminescence), after bronchoalveolar lavages. In particular, it has been shown that intratracheal instillation of silica (50 mg/kg) in rats led to fibrosis characterized by cellular interstitial infiltrates with granulomas, and in AM, it led to 1) an early and continuous increase in 12-O-tetradecanoylphorbol-13-acetate- or zymosan-triggered ROI production (days 1, 3, 14, and 28 post-treatment), and 2) a rise of TNF-alpha mRNA expression and protein secretion on days 3 and 14. A free radical scavenger pretreatment (N-ter-butyl-alpha-phenylnitrone) reversed lung histopathologic changes and decreased AM ROI production and TNF-alpha expression at the level of mRNA. These findings suggest that ROI production is an important primary event determining the silica-induced inflammatory process. ROI may act in an autocrine or paracrine manner and regulate TNF-alpha production by a mechanism promoting gene expression. The critical role of this cytokine in the pathogenesis of silicosis was confirmed by anti-TNF-alpha Ab treatment.

Animals↗
PubMed1995

Interleukin-13 inhibits protein kinase C-triggered respiratory burst in human monocytes. Role of calcium and cyclic AMP.

Interleukin-13 (IL-13), a novel cytokine produced by activated lymphocytes modulates some monocyte functions, but no data is available concerning the signal transduction pathway. We show here, the inhibitory effect of IL-13 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-triggered reactive oxygen intermediate production in human monocytes and the signals involved in this response. Our results show that IL-13 produces rapid and transient phosphoinositide hydrolysis and intracellular Ca2+ mobilization. Furthermore, IL-13 induces intracellular cAMP accumulation through inositol 1,4,5-trisphosphate-dependent Ca2+ mobilization. Metabolic inhibitors were used to relate the first steps in signaling pathways to the inhibitory effect of IL-13 on TPA-triggered reactive oxygen intermediate production. Indeed, inhibitors of phospholipase C (neomycin), intracellular Ca2+ mobilization (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), adenylate cyclase (delta 9-tetrahydrocannabinol), and protein kinase A (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) impair the IL-13 inhibitory response. Altogether these observations indicate that modulatory effect of IL-13 on the TPA-induced oxidative burst is the result of the intracellular cAMP accumulation through an inositol 1,4,5-trisphosphate-induced Ca2+ mobilization-dependent pathway.

Animals↗
PubMed1994

Ca(2+)-dependent activation of phospholipases C and D from mouse peritoneal macrophages by a selective trigger of Ca2+ influx, gamma-hexachlorocyclohexane.

The gamma-isomer of hexachlorocyclohexane (gamma-HCCH), which displays structural homology with inositol, was found to induce an initial influx of Ca2+ in mouse peritoneal macrophages. This was responsible for Ca(2+)-induced Ca2+ release via inositol 1,4,5-trisphosphate produced by phospholipase C and resulted in a sustained increase of cytoplasmic free Ca2+ concentration ([Ca2+]i). Entry of Ca2+ evoked by gamma-HCCH also stimulated phospholipase D, as well as the generation of reactive oxygen species formed by NADPH oxidase. These data suggest that some isoform(s) of phospholipase C, and possibly phospholipase D, can be activated by strictly Ca(2+)-dependent mechanisms. They also describe a new experimental tool allowing to trigger a selective influx of Ca2+. gamma-HCCH could thus be used in further studies aimed to delineate the role of Ca2+ entry in the subsequent activation of other signalling pathways.

Animals↗
PubMed1993

Arachidonic acid metabolism of rat peritoneal macrophages after passive sensitization and allergen challenge.

The aim of our work was to evaluate the effect of passive sensitization of rat peritoneal macrophages (treatment of cells by an anti-ovalbumin IgE-rich serum) on arachidonic acid (AA) metabolism and the impact of specific antigen (ovalbumin) on this process. Compared to a control treatment without serum, the atopic serum and a serum without IgE, used on [3H]AA-labeled macrophages, increased cyclooxygenase and lipoxygenase eicosanoid production. Sera, used prior to [3H]AA incorporation, induced a decrease of 3H-labeled membrane phospholipids and an increase of lipoxygenase metabolites in the [3H]AA incorporation medium. To establish if the serum-induced catabolism of AA differed according to whether it was externally added to the culture medium or incorporated into membrane phospholipids, we studied the eicosanoid secretion of [3H]AA-prelabeled macrophages, treated by the serum and incubated with [14C]AA. It was confirmed that phospholipid-incorporated AA was catabolised following the cyclooxygenase and lipoxygenase pathways and external AA preferentially following the lipoxygenase pathway. The allergen increased the eicosanoid formation of passively sensitized macrophages but not that of cells treated by the serum without IgE. Our data suggest that changes occurring in passive sensitization, on AA mobilization from membrane phospholipids and on AA catabolism, induced by the serum, are independent of IgE and must be taken into consideration on interpreting the allergen effect.

Allergens↗
PubMed1991

Possible implication of arachidonic acid metabolism in the decrease of chemiluminescence production after exposure of murine peritoneal macrophages to diethylnitrosamine and tumour promoter, 12-O-tetradecanoylphorbol-13-acetate.

The effect of the carcinogen diethylnitrosamine (DEN) on prostaglandins (PGs), leukotrienes (LTs) and reactive oxygen intermediates production by murine peritoneal macrophages was assessed. In vitro exposure to DEN (0.8, 1.6 and 8 mM) resulted in a dose-dependent stimulation of the PGs and LTs generation by macrophages. DEN-exposed peritoneal macrophages demonstrated enhanced production of arachidonic acid (AA) metabolites following stimulation with 12-O-tetradecanoylphorbol 13-acetate (TPA) as compared to macrophages stimulated with TPA alone. Studies of [3H]AA release from glycerolipids of prelabelled macrophages and of the distribution of AA metabolites between intra and extracellular compartments indicated that DEN induced de novo synthesis of AA metabolites. The stimulation of AA metabolism by DEN was decreased by H-7 and staurosporine, protein kinase C (PKC) inhibitors, and so could be dependent on PKC activation. The generation of PGs by macrophages after DEN exposure was also inhibited by indomethacin (cyclo-oxygenase inhibitor). DEN at high concentrations (1.6-16 mM) inhibited chemiluminescence production by peritoneal macrophages in a dose-dependent manner, triggered by tumour promoter TPA; lower concentrations (0.8 and 1.2 mM) increased this reactive oxygen intermediates dependent chemiluminescence production induced by TPA. The role of AA metabolism in the alteration of chemiluminescence production by murine peritoneal macrophages treated in vitro with DEN and triggered by TPA has been evaluated by using AA metabolism inhibitors. The stimulation of chemiluminescence by TPA was inhibited by the addition of phospholipase A2 (PLA2) inhibitor, 4-p-BPB; this metabolic inhibitor did not affect the decrease of chemiluminescence production induced by DEN. The cyclo-oxygenase (CO) inhibitor, indomethacin, reversed the inhibition of TPA-induced chemiluminescence caused by DEN. These results suggest that AA and/or a lipoxygenase product can potentiate the reactive oxygen intermediates production by macrophages stimulated by TPA. The CO pathway could be involved in the inhibition by DEN of the reactive oxygen intermediates generating enzyme system. It is suggested that this inhibition could be related to AA metabolites issued from the CO pathway or to DEN oxygenated metabolites issued from the co-oxidation of the DEN by the PGs endoperoxide synthase. These results also raise the problem of macrophage dysfunction by chemical carcinogens and the implication of the CO pathway in this process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

[Bone lymphomas].

Non-hodgkin's lymphomas have benefitted from recent progresses in pathology and from new classifications having a prognostic value. In reference to a case of primary osseous lymphoma, we mention their definition and main characteristics. We stress the good sensitivity of the osseous scintigraphy to detect the osseous localizations of lymphomas. These secondary osseous lymphomas have a poor prognosis. The difficulties of the pathological diagnosis are frequent, but should decrease with the wider use of immunohistochemical marking of the bone or node biopsies.

Adult↗
PubMed1986

[Amyloid pseudotumor disclosing non-secretory myeloma. Ultrastructural demonstration of the role of histiocytes in intratumoral amyloidogenesis].

A 69 year old woman presented initially with an amyloid tumour of the rib. Six months later, she developed a plasma cell tumour of the left acromion diagnosed as an IgG kappa myeloma. Electron microscopy of the initial costal lesion and the plasma cell tumour showed a close resemblance between the dystrophic plasmacytes, which had no morphological evidence of intracytoplasmic amyloid fibrils, and the histiocytes, many of which contained these fibrils and were probable sites of amyloid secretion. This suggests that the costal amyloid tumour was probably the result of transformation of a previous plasma cell tumour, and that intra-tumoural amyloid deposits have the same origin as the systemic amyloidosis observed in cases of multiple myeloma, i.e. the histiocyte.

Acromion↗
PubMed1981

Variations of the digestive absorption kinetics of carbaryl with the nature of the vehicle.

Blood kinetics of 1-naphthyl-N-methyl[14C] carbamate were determined after intravenous injection in DMSO, and after intragastric and intraduodenal administration in DMSO, oil, gum tragacanth and milk. The acetylcholinesterase inhibition and the level of 14C-activity were both determined in the blood over various periods of time. The values of the absorption rate constants after intragastric and intraduodenal administration were found to be: 0.5 h(-1) and 7 h(-1) with DMSO, 0.6 h(-1) and 0.42 h(-1) with oil, 0.13 h(-1) and 0.22 h (-1) with gum tragacanth and 0.10 h(-1) with milk. Appearance of the toxic effect (the inhibition of the acetylcholinesterases) was closely related to the absorption rate constants which themselves depend on the administration vehicle employed.

Animals↗
PubMed1980

Foetal and maternal rat brain acetylcholinesterase: isoenzymes changes following insecticidal carbamate derivatives poisoning.

Pregnant rats (18th day) were orally given insecticidal carbamates with anticholinesterasic properties: 50 mg/kg carbaryl, 0.1 mg/kg aldicarb, 2.5 mg/kg carbofuran and 20 mg/kg pirimicarb. The acetylcholinesterase (AChE) isoenzymes from the brain of mothers and their foetuses were separated by electrophoresis on polyacrylamide ge. The four carbamate derivatives caused a significant lowering of the percentage of the least mobile isoenzyme (isoenzyme 1) in mother. Aldicarb, carbaryl and pirimicarb also caused a significant decrease in the percentage of the first foetal isoenzyme. The second foetal isoenzyme underwent a decrease after treatment with aldicarb or carbofuran. The distribution of the foetal isoenzymes was seen to be different to that of the dams in both control and treated animals. The difference in sensitivity of the cerebral AChE to the insecticides under investigation is thought to depend on differences of the fixation of carbamate derivatives on the foetal and maternal isoenzymes.

Acetylcholinesterase↗