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  • 1
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: 1-Methyl-4-phenyl- 1,2,5,6 -tetrahydropyridine (MPTP) is a chemical that, after injection into experimental animals, including mice and monkeys, causes a degeneration of the nigrostriatal pathway. We carried out experiments designed to study the in vitro oxidation of MPTP by mouse brain mitochondrial preparations. MPTP was actively oxidized by the mitochondrial preparations, with Km and Vmax values very similar to those of benzyl amine, a typical substrate for MAO-B. MPTP was oxidized considerably better than many of its analogs, even those with relatively minor structural changes. Several monoamine oxidase inhibitors (MAOI) were potent inhibitors of MPTP oxidation, and there was a highly significant correlation between the capacity of the MAOI tested to inhibit MPTP oxidation and benzylamine oxidation. There was no correlation between the capacity of the MAOI to inhibit MPTP oxidation and their capacity to inhibit the oxidation of tryptamine, a substrate for MAO-A. In other experiments, MPTP was an excellent substrate for pure MAO-B, prepared from bovine liver. All of these data. combined with the fact that MAO-B inhibitors can protect against MPTP-induced dopami nergic neurotoxicity in vivo. point to an important role for MAO-B in MPTP metabolism in vivo.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Ascorbic acid, sodium ascorbate, and isoascorbic acid (the stereo-isomer of ascorbic acid) inhibited the stereospecific binding of [3H]spiroperidol to neostriatal membrane preparations. Greater inhibitory effects were obtained at intermediate concentrations of the three ascorbic acid analogs (i.e., 0.06 and 0.6 mM) than at higher (6 mM) or lower (0.006 mM) concentrations. In parallel experiments, the three ascorbic acid analogs induced lipid peroxidation, which was also greater at the two intermediate than at higher or lower concentrations. Several known inhibitors of lipid peroxidation, including propyl gallate, butylated hydroxyanisole, butylated hydroxytoluene, α-naphthol, and cobalt chloride, as well as the iron chelating agents EDTA and DETAPAC (diethylenetriaminepentaacetic acid) were able to counteract the effects of the ascorbic acid analogs on both lipid peroxidation and on [3H]spiroperidol binding. These data strongly suggest that an iron-catalyzed lipid peroxidation is responsible for the observed inhibitory effects on binding. In other experiments, neostriatal membrane preparations that were preincubated with ascorbic acid (0.6 mM) and subsequently washed still had greatly diminished capacity to bind [3H]spiroperidol, indicating that ascorbic acid need not be physically present during the binding assay in order to affect binding. This experimental procedure also appears to be a way in which [3H]spiroperidol binding sites can be inactivated and washed free of the inactivating agent.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 41 (1983), S. 0 
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Sodium ascorbate caused an increased lipid peroxidation and a large decrement in [3H]spiroperidol binding in a rat neostriatal membrane preparation (preparation C). Both effects were greater at intermediate (0.05 and 0.5 mM) than at higher or lower ascorbate concentrations. In contrast, in another neostriatal membrane preparation (preparation A), there was no loss of [3H]spiroperidol binding and only a small increase in lipid peroxidation caused by ascorbate. However, both the ascorbate-induced increase in lipid peroxidation and loss of [3H]spiroperidol binding were greatly enhanced in preparation A by the addition of iron salts. In experiments designed to explore reasons for these apparent discrepancies, we discovered that the method of tissue preparation was a critical factor. The ascorbate effects were consistently greater in a tissue preparation which was originally homogenized in an isotonic sucrose medium and centrifuged, and the cell debris discarded (as was done in preparation C), than in one in which the tissue was homogenized in a hypotonic medium and in which no low-speed centrifugation was done (as was done in preparation A). In other experiments, of several cations tested, only ferrous and ferric potentiated the above-described effects of ascorbate. Some ascorbic acid derivatives (e.g., isoascorbic acid) had properties similar to those of ascorbic acid, whereas several reducing agents could, in the presence of added iron salts, cause both a lipid peroxidation and a loss of [3H]spiroperidoI binding. However, the other reducing agents tested (e.g., dithiothreitol) were iess potent in both regards than was ascorbate. In other experiments, several chelating agents (e.g., EDTA) or commonly used inhibitors of lipid peroxidation (e.g., propyl gallate) were able to counteract the effects of ascorbate on lipid peroxidation and on [3H]spiroperidol binding.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to cause a destruction of the dopaminergic nigrostriatal pathway in certain animal species including mice. MPTP and some structurally related analogs were tested in vitro for their capacity to inhibit the uptake of [3H]3,4-dihydroxyphenylethylamine-([3H]DA), [3H]5-hydroxytryptamine ([3H]5-HT), and [3H]γ-aminobutyric acid ([3H]GABA) in mouse neostriatal synaptosomal preparations. MPTP was a very potent inhibitor of [3H]5-HT uptake (IC50 value 0.14 μM), a moderate inhibitor of [3H]DA uptake (IC50 value 2.6 μM), and a very weak inhibitor of [3H]GABA uptake (no significant inhibition observed at 10 μM MPTP). In other experiments, MPTP caused some release of previously accumulated [3H]DA and [3H]5-HT, but in each case MPTP was considerably better as an uptake inhibitor than as a releasing agent. The 4-electron oxidation product of MPTP, i.e., 1-methyl-4-phenyl-pyridinium iodide (MPP+), was a very potent inhibitor of [3H]DA uptake (IC50 value 0.45 μM) and of [3H]5-HT uptake (IC50 value 0.78 μM) but MPP+ was a very weak inhibitor of [3H]GABA uptake. These data may have relevance to the neurotoxic actions of MPTP.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
    ISSN: 1476-4687
    Quelle: Nature Archives 1869 - 2009
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Notizen: [Auszug] Male, Swiss-Webster mice weighing 25-35 g were injected intraperitoneally with pargyline, deprenil, clorgyline, tranylcypromine or nialamide and subsequently received MPTP. As Table 1 shows, 3 days after the last of five injections of MPTP, 30 mg per kg, the mean neostriatal content of dopamine ...
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 38 (1982), S. 378-379 
    ISSN: 1420-9071
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary DETAPAC, an iron-chelating agent, given to male Swiss-Webster mice prior to alloxan, was able to protect the mice from the diabetogenic actions of alloxan. In contrast EDTA, another chelating agent, offered no protection. Possible mechanisms for these effects, including inhibition of hydroxyl radical formation, will be discussed.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Cellular and molecular life sciences 34 (1978), S. 1553-1554 
    ISSN: 1420-9071
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary 4 thiocarbamic acid derivatives inhibited superoxide dismutase (SOD) activity in vitro. Dimethyldithiocarbamate also inhibited tissue SOD in mice in vivo. These data extend previously published results on the inhibitory action of diethyldithiocarbamate on SOD activity.
    Materialart: Digitale Medien
    Standort Signatur Einschränkungen Verfügbarkeit
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