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1.
Toxicity of Dopamine to Striatal Neurons In Vitro and Potentiation of Cell Death by a Mitochondrial Inhibitor 总被引:8,自引:2,他引:6
B. A. McLaughlin †D. Nelson †‡M. Ereciska † M.-F. Chesselet 《Journal of neurochemistry》1998,70(6):2406-2415
Abstract: Intrastriatal injections of the mitochondrial toxins malonate and 3-nitropropionic acid produce selective cell death similar to that seen in transient ischemia and Huntington's disease. The extent of cell death can be attenuated by pharmacological or surgical blockade of cortical glutamatergic input. It is not known, however, if dopamine contributes to toxicity caused by inhibition of mitochondrial function. Exposure of primary striatal cultures to dopamine resulted in dose-dependent death of neurons. Addition of medium supplement containing free radical scavengers and antioxidants decreased neuronal loss. At high concentrations of the amine, cell death was predominantly apoptotic. Methyl malonate was used to inhibit activity of the mitochondrial respiratory chain. Neither methyl malonate (50 µ M ) nor dopamine (2.5 µ M ) caused significant toxicity when added individually to cultures, whereas simultaneous addition of both compounds killed 60% of neurons. Addition of antioxidants and free radical scavengers to the incubation medium prevented this cell death. Dopamine (up to 250 µ M ) did not alter the ATP/ADP ratio after a 6-h incubation. Methyl malonate, at 500 µ M , reduced the ATP/ADP ratio by ∼30% after 6 h; this decrease was not augmented by coincubation with 25 µ M dopamine. Our results suggest that dopamine causes primarily apoptotic death of striatal neurons in culture without damaging cells by an early adverse action on oxidative phosphorylation. However, when combined with minimal inhibition of mitochondrial function, dopamine neurotoxicity is markedly enhanced. 相似文献
2.
3.
From sludge obtained from the sewage digester plant in Stuttgart-Möhringen a strictly anaerobic bacterium was enriched and isolated with methyl chloride as the energy source. The isolate, which was tentatively called strain MC, was nonmotile, gram-positive, and occurred as elongated cocci arranged in chains. Cells of strain MC formed about 3 mol of acetate per 4 mol of CH3Cl consumed, indicating that the organism was a homoacetogenic bacterium fermenting methyl chloride plus CO2 according to:
The organism grew with 2–3% methyl chloride in the gas phase at a doubling time of near 30 h. Dichloromethane was not utilized. The bacterium also grew on carbon monoxide, H2 plus CO2, and methoxylated aromatic compounds. Optimal growth with methyl chloride was observed at 25°C and pH 7.3–7.7. The G+C-content of the DNA was 47.5±1.5%. The methyl chloride conversion appeared to be inducible, since H2 plus CO2-grown cells lacked this ability. From the morphological and physiological characteristics, the isolate could not be affiliated to a known species. 相似文献
4.
The effects of methyl jasmonate and jasmonic acid on uptake of abscisic acid (ABA) by suspension-cultured runner-bean cells and subapical runner-bean root segments have been investigated. Increasing concentrations of methyl jasmonate inhibit ABA uptake by the cultured cells with a K
i of 22±3 M. This is not due to cytoplasmic acidification or to effects on metabolism of ABA, and is not additive with inhibition of radioactive ABA uptake by nonradioactive ABA. Uptake of indol-3-yl acetic acid (IAA) is unaffected by methyl jasmonate. The maximum effect of nonradioactive ABA in inhibiting uptake of radioactive ABA, previously shown to reflect saturation of an ABA carrier, is generally greater than the effect of maximally inhibitory concentrations of methyl jasmonate. Similar results were obtained with root segments, but longer incubation times were necessary to observe inhibitory effects of methyl jasmonate. Demethylation of methyl jasmonate to jasmonic acid does not appear to be required since similar concentrations of jasmonic acid had no observable direct effect on ABA uptake other than that attributable to cytoplasmic acidification. Histidine reagents, a proton ionophore and acidic external pH all affect in parallel the inhibition by methyl jasmonate and nonradioactive ABA of uptake of radioactive ABA by the cultured cells. There is no effect of ABA or nonradioactive methyl jasmonate on uptake of radioactive methyl jasmonate by the cultured cells. It is proposed that methyl jasmonate interacts with the ABA carrier. Various models for this interaction are discussed.Abbreviations ABA
abscisic acid
- DMO
5,5-dimethyloxazolidine-2,4-dione
- IAA
indol-3-yl acetic acid 相似文献
5.
Experimental Methyl Mercury Neurotoxicity: Locus of Mercurial Inhibition of Brain Protein Synthesis In Vivo and In Vitro 总被引:2,自引:1,他引:1
Brain cell-free protein synthesis is inhibited by methyl mercury chloride (MeHg) following in vivo or in vitro administration. In this report, we have identified the locus of mercurial inhibition of translation. Intraperitoneal injection of MeHg (40 nmol/g body wt) induced variable inhibition of amino acid incorporation into the post-mitochondrial supernatant (PMS) harvested from the brain of young (10-20-day-old) rats. No mercurial-induced disaggregation of brain polyribosomes nor change in the proportion of 80S monoribosomes was detected on sucrose density gradients. No difference in total RNA was found in the PMS. Initiation complex formation was stimulated by MeHg, as detected by radiolabelled methionine binding to 80S monoribosomes following continuous sucrose density gradient centrifugation. After micrococcal nuclease digestion of endogenous mRNA, both in vivo and in vitro MeHg inhibited polyuridylic acid-directed incorporation of [3H]phenylalanine. However, the in vivo inhibition was no longer observed when [3H]phenylalanyl-tRNAPhe replaced free [3H]phenylalanine in the incorporation assay. The formation of peptidyl[3H]puromycin revealed no difference from controls. There was significant mercurial inhibition of phenylalanyl-tRNA Phe synthetase activity in pH 5 enzyme fractions derived from brain PMS of MeHg-poisoned rats. These experiments revealed that the apparent MeHg inhibition of brain translation in vivo and in vitro is due primarily to perturbation in the aminoacylation of tRNA and is not associated with defective initiation, elongation, or ribosomal function. 相似文献
6.
Synthesis of methyl
-Ribose was converted into methyl
and this, on tin-mediated allylation, gave a mixture of the 2-O-allyl and 3-O-allyl derivatives which were separated by chromatography. The more polar isomer was characterised as the 3-O-allyl derivative after conversion via
(which was also synthesised from
) into the known
. Methyl
was converted into methyl
via methyl
. 相似文献
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7.
We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of -oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-14C]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-14C]PA from 0.67 to 5.7. The incorporation rate coefficient, k*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-11C]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity. 相似文献
8.
The methyl chloride metabolism of the homoacetogenic, methyl chloride-utilizing strain MC was investigated with cell extracts and cell suspensions of the organism. Cell extracts were found to contain all enzyme activities required for the conversion of methyl chloride or of H2 plus CO2 to acetate. They catalyzed the dechlorination of methyl chloride with tetrahydrofolate as the methyl acceptor at a rate of 20 nmol/min × mg of cell protein. Also, the O-demethylation of vanillate with tetrahydrofolate could be measured at a rate of 40 nmol/min × mg. Different enzyme systems appeared to be responsible for the dehalogenation of CH3Cl and for the O-demethylation of methoxylated aromatic compounds, since cells grown with methoxylated aromatic compounds exhibited a significantly lower activity of CH3Cl conversion than methyl chloride grown cells and vice versa. In addition, ammonium thiocyanate (5 mM) completely inhibited CH3Cl dechlorination, whereas the consumption of vanillate was not affected significantly. The data were taken to indicate, that the methyl chloride dehalogenation is catalyzed by a specific, inducible enzyme present in strain MC, and that tetrahydrofolate rather than the corrinoid-protein involved in acetate formation is the primary acceptor of the methyl group in the dechlorination reaction. 相似文献
9.
Field application of vesicular-arbuscular mycorrhizal fungi improved garlic yield in disinfected soil 总被引:1,自引:0,他引:1
The production of certified garlic propagation material requires measures to be taken against pathogenic nematodes. Methyl
bromide (MB) may be used for this purpose, but is known to cause stunting in Allium spp. Vesicular-arbuscular mycorrhizal (VAM) fungal inoculum was applied to the planting furrow after MB treatment. VAM-inoculated
plants were larger, had more green leaves, an increased photosynthesis rate, especially at low light intensities, and higher
fresh and dry weights than plants in uninoculated plots. The mean bulb weights from uninoculated and VAM-treated plots were
27 g and 51 g respectively. The native or an improved VAM population should be reintroduced after soil disinfection to ensure
satisfactory garlic yields.
Accepted: 15 January 1997 相似文献
10.
N. Sewald W. Hollweck K. Mütze C. Schierlinger L. C. Seymour K. Gaa K. Burger B. Koksch H. D. Jakubke 《Amino acids》1995,8(2):187-194
Summary Methodology for the synthesis and incorporation of-trifluoromethyl substituted amino acids into N- and C-terminal position of peptides is described. The incorporation of-trifluoromethyl substituted amino acids into strategical positions of peptides enhances proteolytic stability and lipophilicity. Furthermore, it improves transport rates in vivo and permeability through certain body barriers. 相似文献