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981.
Emanuela Santini Cristina Alcacer†‡§ Silvia Cacciatore Myriam Heiman¶ Denis Herv醇§ Paul Greengard¶ Jean-Antoine Girault†‡§ Emmanuel Valjent†‡§ Gilberto Fisone 《Journal of neurochemistry》2009,108(3):621-633
In the dopamine-depleted striatum, extracellular signal-regulated kinase (ERK) signaling is implicated in the development of l -DOPA-induced dyskinesia. To gain insights on its role in this disorder, we examined the effects of l -DOPA on the state of phosphorylation of ERK and downstream target proteins in striatopallidal and striatonigral medium spiny neurons (MSNs). For this purpose, we employed mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoters for the dopamine D2 receptor ( Drd2 -EGFP mice) or the dopamine D1 receptor ( Drd1a -EGFP mice), which are expressed in striatopallidal and striatonigral MSNs, respectively. In 6-hydroxydopamine-lesioned Drd2 -EGFP mice, l -DOPA increased the phosphorylation of ERK, mitogen- and stress-activated kinase 1 and histone H3, selectively in EGFP-negative MSNs. Conversely, a complete co-localization between EGFP and these phosphoproteins was observed in Drd1a -EGFP mice. The effect of l -DOPA was prevented by blockade of dopamine D1 receptors. The same pattern of activation of ERK signaling was observed in dyskinetic mice, after repeated administration of l -DOPA. Our results demonstrate that in the dopamine-depleted striatum, l -DOPA activates ERK signaling specifically in striatonigral MSNs. This regulation may result in ERK-dependent changes in striatal plasticity leading to dyskinesia. 相似文献
982.
Functional expression of mammalian receptors and membrane channels in different cells 总被引:1,自引:0,他引:1
Eifler N Duckely M Sumanovski LT Egan TM Oksche A Konopka JB Lüthi A Engel A Werten PJ 《Journal of structural biology》2007,159(2):179-193
In native tissues, the majority of medically important membrane proteins is only present at low concentrations, making their overexpression in recombinant systems a prerequisite for structural studies. Here, we explore the commonly used eukaryotic expression systems-yeast, baculovirus/insect cells (Sf9) and Semliki Forest Virus (SFV)/mammalian cells-for the expression of seven different eukaryotic membrane proteins from a variety of protein families. The expression levels, quality, biological activity, localization and solubility of all expressed proteins are compared in order to identify the advantages of one system over the other. SFV-transfected mammalian cell lines provide the closest to native environment for the expression of mammalian membrane proteins, and they exhibited the best overall performance. But depending on the protein, baculovirus-infected Sf9 cells performed almost as well as mammalian cells. The lowest expression levels for the proteins tested here were obtained in yeast. 相似文献
983.
984.
Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation 总被引:1,自引:0,他引:1
Sempértegui F Díaz M Mejía R Rodríguez-Mora OG Rentería E Guarderas C Estrella B Recalde R Hamer DH Reeves PG 《Helicobacter》2007,12(1):43-48
BACKGROUND: Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. METHODS: Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. RESULTS: H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). CONCLUSIONS: The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations. 相似文献
985.
Background
Along the chromosome of the obligate intracellular bacteria Protochlamydia amoebophila UWE25, we recently described a genomic island Pam100G. It contains a tra unit likely involved in conjugative DNA transfer and lgrE, a 5.6-kb gene similar to five others of P. amoebophila : lgrA to lgrD, lgrF. We describe here the structure, regulation and evolution of these proteins termed LGRs since encoded by "Large G+C-Rich" genes. 相似文献986.
Tarze A Dauplais M Grigoras I Lazard M Ha-Duong NT Barbier F Blanquet S Plateau P 《The Journal of biological chemistry》2007,282(12):8759-8767
Administration of selenium in humans has anticarcinogenic effects. However, the boundary between cancer-protecting and toxic levels of selenium is extremely narrow. The mechanisms of selenium toxicity need to be fully understood. In Saccharomyces cerevisiae, selenite in the millimolar range is well tolerated by cells. Here we show that the lethal dose of selenite is reduced to the micromolar range by the presence of thiols in the growth medium. Glutathione and selenite spontaneously react to produce several selenium-containing compounds (selenodiglutathione, glutathioselenol, hydrogen selenide, and elemental selenium) as well as reactive oxygen species. We studied which compounds in the reaction pathway between glutathione and sodium selenite are responsible for this toxicity. Involvement of selenodiglutathione, elemental selenium, or reactive oxygen species could be ruled out. In contrast, extracellular formation of hydrogen selenide can fully explain the exacerbation of selenite toxicity by thiols. Indeed, direct production of hydrogen selenide with D-cysteine desulfhydrase induces high mortality. Selenium uptake by S. cerevisiae is considerably enhanced in the presence of external thiols, most likely through internalization of hydrogen selenide. Finally, we discuss the possibility that selenium exerts its toxicity through consumption of intracellular reduced glutathione, thus leading to severe oxidative stress. 相似文献
987.
Global chromatin compaction limits the strength of the DNA damage response 总被引:4,自引:0,他引:4
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Murga M Jaco I Fan Y Soria R Martinez-Pastor B Cuadrado M Yang SM Blasco MA Skoultchi AI Fernandez-Capetillo O 《The Journal of cell biology》2007,178(7):1101-1108
In response to DNA damage, chromatin undergoes a global decondensation process that has been proposed to facilitate genome surveillance. However, the impact that chromatin compaction has on the DNA damage response (DDR) has not directly been tested and thus remains speculative. We apply two independent approaches (one based on murine embryonic stem cells with reduced amounts of the linker histone H1 and the second making use of histone deacetylase inhibitors) to show that the strength of the DDR is amplified in the context of "open" chromatin. H1-depleted cells are hyperresistant to DNA damage and present hypersensitive checkpoints, phenotypes that we show are explained by an increase in the amount of signaling generated at each DNA break. Furthermore, the decrease in H1 leads to a general increase in telomere length, an as of yet unrecognized role for H1 in the regulation of chromosome structure. We propose that slight differences in the epigenetic configuration might account for the cell-to-cell variation in the strength of the DDR observed when groups of cells are challenged with DNA breaks. 相似文献
988.
Disseminating and facilitating access to science-based information is a necessity to enable the public to make informed decisions about appropriate uses of biotechnology products. It is also one of the major objectives of Co-Extra, a European-funded project addressing co-existence of genetically modified organisms and non-genetically modified organisms in Europe and their traceability. To this end, a dynamic and interactive website has been developed as the core element of the Co-Extra external communication strategy. This website has been designed to make it attractive and accessible to a large audience in a very simple and practical manner, building on practical experiences gained in the development of other websites related to biotechnology and genetically modified organisms. The website delivers popularized information for the general public as well as scientific data meant primarily for the more expert readers. It also provides for various permanent tools allowing multidirectional interaction with its visitors. Content is displayed using a web-based platform, based on a sophisticated Content Management System. First results indicate a high level of interest from the general public and from experts, showing that the content of this website can contribute by communicating science-based information to improve awareness and understanding of biotechnology. 相似文献
989.
990.
This study investigates the effects of subchronic exposure to organophosphate insecticide Malathion (Fyfanon 50 EC 500 g/l) of commercial grade. It was administered intragastrically by stomach tube in the amount of 1 ml of corn oil containing 100 mg/kg body weight (BW) daily for 32 days. At the end of the experiment, acetylcholinesterase activity (AChE), haematocrit value, haemoglobin content, and blood glucose concentration were estimated. The liver and the skeletal muscle were removed to determine hepatic and muscular glycogen, hepatic proteins and lipids contents. No sign of toxicity was observed until the end of experiment. No significant change in the haematocrit value was observed, in spite of the significant increase in haemoglobin content, which can be considered as an adaptive situation in order to guarantee a good oxygenation in response to pulmonary damage induced following subchronic exposure to organophosphorus compound. Malathion intoxication decreased significantly hepatic proteins and lipid contents that could be associated to liver gluconeogenesis. This result was coupled with a significant decrease in muscular glycogen rate, which indicates a stimulated glycogenolysis in favour of glucose release into the blood until reaching hyperglycaemia. Several studies indicate that hyperglycaemia is temporary, which is probably due to a stimulated glycogenesis that increases hepatic glycogen deposition and return of glucose to control levels, as demonstrated in our study. One possible explanation for these results could be the turnover of glucose by a succession between its release via glycogenolysis and gluconeogenesis, which involves abnormal hyperglycaemia, and its storage via glycogenesis in subchronic exposure to malation. 相似文献