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F Cattabeni

Publications and source records attributed to F Cattabeni.

At least 163 records · Page 9Linked to original sources
PubMed1987

Protein phosphorylation in rat pineal gland and its regulation in supersensitive and subsensitive states.

The phosphorylation of specific proteins in pineal homogenate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Cyclic AMP had the capacity to stimulate in a dose-dependent manner the incorporation of 32P in protein bands of apparent molecular weights 59K, 56K, and 35K with a maximal effect at 1 microM. On the other hand, calcium alone did not induce a marked increase in 32P incorporation with the exception of a dose-dependent phosphorylation of a 46K protein with a peak effect at 0.2 mM calcium concentration. The addition of exogenous calmodulin enhanced 32P incorporation in proteins migrating in the 62K and 52K regions, an effect that was antagonized by the calmodulin inhibitor trifluoperazine. However, also under these conditions, the stimulation of pineal protein phosphorylation was rather weak compared to that observed in other brain areas. In an attempt to investigate the functional changes of these biochemical processes during environmental lighting and adrenergic stimulation, it was found that the administration of (-)-isoproterenol (5 mg/kg, s.c.), a beta-receptor agonist, induced a clear-cut enhancement of 32P incorporation into the cyclic AMP-sensitive 59K and 56K proteins only in animals exposed for 18 h to the light, whereas it was almost ineffective in those kept in the dark for the same period. This effect was antagonized by (-)-propranolol pretreatment (20 mg/kg), suggesting that the changes in cyclic AMP-dependent protein phosphorylation observed in supersensitive pineals may represent a beta-receptor mediated process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Differential effect of ganglioside GM1 on rat brain phosphoproteins: potentiation and inhibition of protein phosphorylation regulated by calcium/calmodulin and calcium/phospholipid-dependent protein kinases.

The monosialoganglioside GM1 displays complex effects on protein phosphorylation of rat cerebral cortex membrane preparations. The exogenous ganglioside at a concentration of 350 microM in absence of calcium only stimulated the phosphorylation of a protein of MW = 64,000. In presence of 1 mM calcium a twofold effect is observed irrespective of the phosphoprotein considered. In particular there is an enhancement of 32P incorporation in four major phosphoproteins of MW = 160,000, 140,000, 64,000 and 50,000 in presence of GM1 compared with that observed with calcium alone. The maximal stimulating effect is achieved with a ganglioside concentration of 35 microM. This effect is inhibited by the addition of 100 microM trifluoperazine (TFP), a phenothiazine known to inhibit calmodulin and protein kinase-C activities. These four proteins represent the major substrates for the calcium/calmodulin-dependent protein kinase with the MW = 64,000 and 50,000 proteins co-migrating with the autophosphorylated subunits of this enzyme. In addition, the ganglioside inhibited the phosphorylation of three proteins with MW = 86,000, 20,000 and 14,000. The electrophoretic properties of these phosphoproteins are similar to the autophosphorylated form of protein kinase-C and to the rat myelin basic proteins, respectively. The effect of the ganglioside on their phosphorylation is not influenced by TFP. Finally, a protein with an apparent molecular weight of 46,000 shows also an increased phosphorylation in presence of GM1. The reported results indicate that exogenous GM1 can have profound effects on different kinases such as the calcium/calmodulin dependent protein kinase, the protein kinase-C and also some unknown calcium-independent protein kinases.

Animals↗
PubMed1987

Analogues of benzamide containing a sulfur atom as poly(ADP-ribose) transferase inhibitors.

Structural analogues of benzamide (BA) containing a sulfur atom were tested for their ability to inhibit the enzyme poly(ADP-ribose)transferase (ADPRT) in cultured Chinese Hamster Ovary (CHO) cells. These compounds were benzene sulfonamide (BSA), thiobenzamide (TB) and 3-thiophene carboxamide (TCA) and their activity was compared with that of benzamide in a number of experimental systems. Results have shown that substitution of the carboxamide function with a sulfonamide group produces an almost complete loss of the enzyme inhibiting activity. Also inactive was TB which however was found to display inhibition of the DNA damaging effect of hydrogen peroxide, thus suggesting a hydroxyl radical scavenging effect of TB. TCA, an isostere of BA, produced some inhibition of ADPRT, although its activity was markedly lower than that of the parental drug. Therefore, these results indicate that: 1) ADPRT inhibiting activity is inverse function of dipole moments, hydrogen bonding strength and steric hindrance of the amide functional group and 2) substitution of benzene with thiophene results in a substantial reduction of the enzyme inhibiting activity.

Animals↗
PubMed1987

Interaction of some 2-hydroxybenzylpiperidines with dopamine receptors.

Some N-alkyl derivatives of 2-(3-hydroxybenzyl)piperidine and of 2-(3,4-dihydroxybezyl)piperidine were synthesized and evaluated pharmacologically in vitro by competition with [3H]spiperone for binding to a homogenized rat striatal tissue, and for ability to stimulate adenylate cyclase. The N-methyl-2-(3,4-dihydroxybenzyl)piperidine shows a fairly good affinity for the D-2 dopamine receptor. The N-alkyl 2-(3,4-dihydroxybenzyl)piperidines produce a faible stimulation of adenylate cyclase activity.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Chilling followed by incubation at 37 degrees C causes a reduction in NAD+ levels which can be prevented by the poly(ADP-ribose)transferase inhibitor 3-aminobenzamide.

The exposure of cells for 60 min to a serum free medium at ice temperature followed by a return to normal culture conditions (30 min at 37 degrees C) caused a dramatic decrease in NAD+ levels. This decrease in NAD+ was prevented by 3-aminobenzamide. Alkaline elution analysis of DNA from cultures that were sisters to the ones utilized for measuring cellular NAD+ content revealed an absence of DNA breakage. These data suggest that poly(ADP-ribose)transferase may be induced in conditions not involving DNA fragmentation. The induction of this enzyme could therefore represent a cellular emergency reaction and not just a response to DNA damage.

Animals↗
PubMed1986

1,3 dideazaadenosine is a mitogen for cultured mammalian cells.

The effect of 1,3-dideazaadenosine (c1,3Ado) on DNA synthesis and rate of proliferation was measured in various mammalian cell lines. Vero, HeLa, CHO and SV40 3T3 cells displayed equal sensitivity to the stimulatory effect of the drug. Further experiments performed with Vero cells have indicated that the action of c1,3Ado was prompt, cell density dependent and did not result from an increased cell membrane permeability to exogenous labelled thymidine. c1,3Ado increased cell proliferation in 6 different normal or transformed cell lines. This data indicates that c1,3Ado displays mitogenic properties in cultured mammalian cells.

Animals↗
PubMed1986

Analytical procedures to detect 2,3,7,8-TCDD at Seveso after the industrial accident of July 10, 1976.

The analytical procedures used at Seveso (Milan, Italy) for the determination of 2,3,7,8-TCDD, and some isomers, in biological and environmental samples are reviewed in this paper. During the emergency period, up until the first 10 days of August, the extracts, mostly from soil or vegetation samples, were evaporated to dryness and then mixed with less than or equal to 10-ml solvent. Of these solutions, aliquots up to 10 microliter were injected into a low-resolution gas chromatograph (GC) combined with a low-resolution mass spectrometer (MS). Analytical sensitivity for vegetation and soil was less than 10 ppb and approximately 100 ppt, respectively--sufficient for the early mapping of the most heavily contaminated territory. After the emergency period, the greatest improvement in environmental sample analysis was the introduction of cleanup procedure which greatly reduced the presence of unwanted material in samples. Cleanup was followed by the complete removal of the solvent. Dry samples could be taken up with rather small volumes (greater than or equal to 0.1 ml) of solvent, of which an aliquot was used for GC-MS analysis. The instrumental setup was kept as above. For animal samples, extraction entailed preliminary alkaline digestion followed by a number of cleanup steps. The final dry sample was taken to desired volume by adding solvent (greater than or equal to 0.1 ml), of which a few microliters were injected in GC-MS apparatuses. Detection thresholds improved markedly and were less than 10 ppt for agricultural soil and sediment, less than or equal to 0.05 ppt for water, in the range of 60 to 200 ppt for air dust, less than 10 ng/m2 and 10 ppt for wipe and scrape tests, respectively, less than 50 ppt for vegetation, and 250 ppt for biological substrata. Major later improvements in TCDD assay were the use of high-resolution gas chromatography (hrGC-MS), in some cases combined with high-resolution mass spectrometry (hrGC-hrMS). This provided greater specificity, sometimes accompanied by a very marked increase in detection sensitivity.

Accidents, Occupational↗
PubMed1986

Functional and biochemical modifications of lung beta-adrenoreceptors after in vivo desensitization: prevention by indomethacin.

Desensitization of lung beta-adrenoreceptors induced by 4 day in vivo isoprenaline administration to rats has been investigated both from a functional a biochemical viewpoint. Chronic isoprenaline treatment significantly reduced the relaxing activity of the beta-agonist when tested ex vivo in lung parenchymal strips and also impaired the adenylate-cyclase system. Moreover, the desensitization procedure decreased by about 30% beta-adrenoreceptor number. In vivo indomethacin treatment prevented the loss of pharmacological responsiveness of the tissue to isoprenaline and restored basal adenylate-cyclase activity. These data indicate that in vivo isoprenaline administration actually leads to pulmonary beta-adrenoreceptor desensitization. The involvement of arachidonic acid metabolites in this phenomenon is also discussed.

Adenylyl Cyclases↗
PubMed1986

Induction of DNA breakage and suppression of DNA synthesis by the OH radical generated in a Fenton-like reaction.

The effect of the OH radical, generated in a Fenton-like reaction, on DNA structure and function was studied in a monkey kidney cell line (Vero). DNA single strand breaks were detected following exposure to 10- 100 microM concentrations of H2O2 on ice. These breaks were repaired very rapidly, and addition of the poly (ADP-ribose) transferase inhibitor, 3-aminobenzamide, resulted in an accumulation of breaks. DNA synthesis was inhibited at concentrations as high as 1- 30 mM, this effect also being reversible in approximately 60 min. 3-aminobenzamide did not affect the rate of DNA synthesis inhibition by H2O2.

Animals↗
PubMed1986

Microencephalic rats as a model for cognitive disorders.

The administration of the antimitotic compound methylazoxymethanol (MAM) to gestating rats induces a dose-dependent atrophy of specific brain areas in the offspring. This specificity is strictly dependent upon the time of MAM administration. When given at day 15 of gestation only the cortex, hippocampus, and striatum are affected, whereas when given to rat pups at postnatal day 1, the atrophy is apparent only in the cerebellum. The microencephalic offspring of dams treated at day 15 of gestation develop normally to adulthood, without manifest signs of this profound telencephalic contraction. Behavioral abnormalities are observable when subjecting these animals to tests that involve learning. The deficit in associative behavior might have its anatomical and neurochemical counterpart in the disruption of the neuronal circuitry in the neocortex, where about 50% of interneurons are absent in layers II-IV after a dose of MAM of 25 mg/kg. Loss of intrinsic neurons occurs also in the striatum, as revealed by neurochemical and pharmacological analysis. Indeed, MAM rats show a reduced dopamine-dependent adenylate cyclase activity and a reduced motor stimulation in response to dopaminergic stimulants. MAM rats are therefore an interesting animal model of chronic brain damage induced transplacentally, which could serve for studying adaptive mechanisms of the CNS to this damage and its pharmacological manipulation.

Animals↗
PubMed1986

Differences in the effects of Hg(II) on DNA repair induced in Chinese hamster ovary cells by ultraviolet or X-rays.

The effect of relatively nontoxic levels of HgCl2 on semiconservative DNA synthesis and on DNA repair induced following treatment of intact cells with X-ray or ultraviolet (UV) light has been studied in cultured Chinese hamster ovary cells. In the presence of 1 microM HgCl2 the repair of DNA strand breaks induced by 450 rads of X-rays was reduced by 37%. If a treatment of 2.5 microM HgCl2 was given to cells for only 15 min prior to a 450-rad irradiation, the rate of repair was reduced even further with only 25% of the breaks being repaired in the first hour following irradiation. When comparable treatments of HgCl2 were given to Chinese hamster ovary cells in conjunction with UV irradiation there was no significant effect on either the number of initial strand scission events or the return to high molecular weight DNA following completion of repair. Only after exposure of cells to toxic levels of Hg(II) (higher concentrations or longer treatments) was there measurable inhibition of UV-induced repair as evidenced by a reduced rate of ligation of DNA to a high molecular weight form. Inhibition of the endonuclease step of UV repair was not observed since Hg(II)-treated cells exhibited the same level of strand scission immediately following UV as cells not treated with Hg(II). The observed differences in the effects of Hg(II) on two pathways for DNA repair indicate that the potential for synergistic action between Hg(II) and other DNA damaging agents will be determined in part by the repair pathways induced by each agent. Additionally, it was found that inhibition of semiconservative synthesis also occurs at low concentrations of HgCl2 similar to those affecting X-ray-induced repair. The presence of Hg-DNA adducts in the DNA at these concentrations may cause a reduction in normal replication to facilitate DNA repair.

Animals↗
PubMed1985

Inhibition of nucleic acids and protein synthesis by deazaadenosine derivatives: a study on structure-activity relationships.

The effect of four deaza-analogues of adenosine on the synthesis of nucleic acids and proteins was investigated in monkey kidney cell line Vero. Cells in exponential growth phase were exposed for two hours to 1, 3 or 10 microM concentrations of 1-deazaadenosine (c1Ado), 3-deazaadenosine (c3Ado), 7-deazaadenosine (c7Ado) or 1,3-dideazaadenosine (c1,3Ado) in a serum free medium; the rate of macromolecules synthesis was estimated after one hour pulse treatment with radiolabelled precursors. At the concentrations used, c1Ado and c3Ado produced no or very little change in the rate of macromolecules synthesis: c1Ado slightly increased RNA synthesis whereas c3Ado was a weak inhibitor of DNA synthesis. Conversely, c7Ado was a potent inhibitor of macromolecules synthesis. Two hours of drug exposure at a concentration of 10 microM, resulted in a 40-50% inhibition in DNA, RNA and protein synthesis rates. c1,3Ado did not significantly affect RNA or protein metabolism but produced a dramatic increase in DNA synthesis. No DNA breaks could be detected in cells exposed to the agents tested in this study.

Animals↗
PubMed1985

Arachidonic acid metabolites induce beta-adrenoceptor desensitization in rat lung in vitro.

The possible involvement of arachidonic acid (AA) or its metabolites in beta-adrenoceptor desensitization has been studied in rat lung parenchyma both from a functional and a biochemical point of view. In vitro perfusion of rat lungs with AA (3 X 10(-5)M for 20 min) reduced the relaxant effect of isoproterenol (ISO) on lung parenchymal strips, shown by a shift to the right of ISO dose-response curve, similar to that obtained using desensitizing concentration of specific beta-agonist. Moreover, AA treatment reduced the capacity of ISO to stimulate adenylate-cyclase activity, whereas the number of beta-receptor binding sites was not significantly modified. Inhibition of cyclo-oxygenase pathway by indomethacin (INDO) (1.5 X 10(-5)M) prevented both the loss of ISO-relaxing capacity and the decrease of adenylate-cyclase activity induced by AA treatment. In order to support the role of eicosanoids in beta-adrenoceptor desensitization, changes of endogenous free AA levels have also been studied in lung homogenates. Perfusion of rat lung with ISO (10(-6)M for 20 min) decreased by about 50% the levels of free AA and the pretreatment with BW755C (9 X 10(-5)M), a lipo- and cyclo-oxygenase inhibitor, prevented this phenomenon. On the basis of these results, we suggest that the activation of AA cascade is actually involved in beta-adrenoceptor desensitization in lung tissues with a possible interference at the site beyond the drug-receptor interaction.

Adenylyl Cyclases↗
PubMed1985

Adriamycin does not affect the repair of X-ray induced DNA single strand breaks.

The ability of the antitumor antibiotic adriamycin (Ad) to inhibit the rejoining of DNA single strand breaks produced by X-rays was investigated in cultured cells. Chinese hamster ovary (CHO) cells were given 400 rad and were allowed to repair in the presence or absence of Ad for 60 min at 37 degrees C. The drug did not affect the ability of cells to repair DNA breaks and residual breaks found after the repair period were attributable to those induced by Ad alone.

Animals↗