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排序方式: 共有81条查询结果,搜索用时 15 毫秒
1.
Nitric oxide triggers the toxicity due to glutathione depletion in midbrain cultures through 12-lipoxygenase 总被引:5,自引:0,他引:5
Canals S Casarejos MJ de Bernardo S Rodríguez-Martín E Mena MA 《The Journal of biological chemistry》2003,278(24):21542-21549
Glutathione (GSH) depletion is the earliest biochemical alteration shown to date in brains of Parkinson's disease patients. However, data from animal models show that GSH depletion by itself is not sufficient to induce nigral degeneration. We have previously shown that non-toxic inhibition of GSH synthesis with l-buthionine-(S,R)-sulfoximine in primary midbrain cultures transforms a nitric oxide (NO) neurotrophic effect, selective for dopamine neurons, into a toxic effect with participation of guanylate cyclase (GC) and cGMP-dependent protein kinase (PKG) (Canals, S., Casarejos, M. J., de Bernardo, S., Rodríguez-Martín, E., and Mena, M. A. (2001) J. Neurochem. 79, 1183-1195). Here we demonstrate that arachidonic acid (AA) metabolism through the 12-lipoxygenase (12-LOX) pathway is also central for this GSH-NO interaction. LOX inhibitors (nordihydroguaiaretic acid and baicalein), but not cyclooxygenase (indomethacin) or epoxygenase (clotrimazole) ones, prevent cell death in the culture, even when added 10 h after NO treatment. Furthermore, the addition of AA to GSH-depleted cultures precipitates a cell death process that is indistinguishable from that initiated by NO in its morphology, time course, and 12-LOX, GC, and PKG dependence. The first AA metabolite through the 12-LOX enzyme, 12-hydroperoxyeicosatetraenoic acid, induces cell death in the culture, and its toxicity is greatly enhanced by GSH depletion. In addition we show that if GSH synthesis inhibition persists for up to 4 days without any additional treatment, it will induce a cell death process that also depends on 12-LOX, GC, and PKG activation. In this study, therefore, we show that the signaling pathway AA/12-LOX/12-HPETE/GC/PKG may be important in several pathologies in which GSH decrease has been documented, such as Parkinson's disease. The potentiating effect of NO over such a signaling pathway may be of relevance as part of the cascade of events leading to and sustaining nerve cell death. 相似文献
2.
The role of astroglia on the survival of dopamine neurons 总被引:5,自引:0,他引:5
Mena MA de Bernardo S Casarejos MJ Canals S Rodríguez-Martín E 《Molecular neurobiology》2002,25(3):245-263
Glial cells play a key role in the function of dopamine (DA) neurons and regulate their differentiation, morphology, physiological
and pharmacological properties, survival, and resistance to different models of DA lesion. Several studies suggest that glial
cells may be important in the pathogenesis of Parkinson’s disease (PD), a common neurodegenerative disorder characterized
by degeneration of the nigrostriatal DA system. In this disease the role of glia could be due to the excessive production
of toxic products such as nitric oxide (NO) or cytokines characteristic of inflammatory process, or related to a defective
release of neuroprotective agents, such as small antioxidants with free radical scavenging properties or peptidic neurotrophic
factors. 相似文献
3.
Zagórska A Pozo-Guisado E Boudeau J Vitari AC Rafiqi FH Thastrup J Deak M Campbell DG Morrice NA Prescott AR Alessi DR 《The Journal of cell biology》2007,176(1):89-100
Mutations within the WNK1 (with-no-K[Lys] kinase-1) gene cause Gordon's hypertension syndrome. Little is known about how WNK1 is regulated. We demonstrate that WNK1 is rapidly activated and phosphorylated at multiple residues after exposure of cells to hyperosmotic conditions and that activation is mediated by the phosphorylation of its T-loop Ser382 residue, possibly triggered by a transautophosphorylation reaction. Activation of WNK1 coincides with the phosphorylation and activation of two WNK1 substrates, namely, the protein kinases STE20/SPS1-related proline alanine-rich kinase (SPAK) and oxidative stress response kinase-1 (OSR1). Small interfering RNA depletion of WNK1 impairs SPAK/OSR1 activity and phosphorylation of residues targeted by WNK1. Hyperosmotic stress induces rapid redistribution of WNK1 from the cytosol to vesicular structures that may comprise trans-Golgi network (TGN)/recycling endosomes, as they display rapid movement, colocalize with clathrin, adaptor protein complex 1 (AP-1), and TGN46, but not the AP-2 plasma membrane-coated pit marker nor the endosomal markers EEA1, Hrs, and LAMP1. Mutational analysis suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle localization. Our observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress. 相似文献
4.
Summary We study the leg morphology and feeding postures of two subspecies of the Blue Tit (Parus caeruleus; Tenerife island and the Iberian Peninsula) and the Coal Tit (Parus ater; Iberian Peninsula). We search for evidence supporting the hypothesis of convergent evolution in morphological and ecological traits and we discuss the role of ecomorphological hypotheses as predictors of foraging differences at the intraspecific level. To overcome the problems introduced by environmental characteristics not related to locomotion and competition, we make observations under controlled situations to manage food quality and food access. We determine that the island Blue Tit has a longer tarsometatarsus, larger foot span and a more proximal insertion of the tibialis cranialis muscle (flexor of the tarsometatarsus) than the mainland Blue Tit. These morphological differences are consistent with the more frequent use of hanging and clinging head-up postures by the Iberian Blue Tit. Several ecomorphological hypotheses obtained at the interspecific level with other taxa, have proved to be of high predictive value for explaining ecological differences considering morphological evolution. The Tenerife Blue Tit and the Iberian Coal Tit clearly show close convergence in both feeding postures and leg structure, although some differences in morphology were found between these two species. Convergence in foraging methods between the island Blue Tit and the mainland Coal Tit can be explained without considering current interspecific competition as a determinant of niche space. 相似文献
5.
Diana Reimers Antonio S Herranz Juan José Díaz-Gil María Val T Lobo Carlos L Paíno Raquel Alonso María José Asensio Rafael Gonzalo-Gobernado Eulalia Bazán 《The journal of histochemistry and cytochemistry》2006,54(4):457-465
Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and may be useful for neuroregenerative therapies. The aim of this work was to investigate the effects of the intrastriatal (IS) infusion of LGF in the 6-hydroxydopamine rat model of Parkinson's disease. Tyrosine hydroxylase-positive innervation was significantly increased in the dopamine-denervated striatum of rats receiving intrastriatal LGF infusions (160 ng/day/rat x 15 days) as compared with a vehicle-infused group. There was no evidence of dopaminergic neurogenesis in the striatum or substantia nigra in any experimental group at the times studied. However, in those animals undergoing IS-LGF infusion for 48 hr, we found a significant increase in both microglial proliferation and in the number of microglial cells that acquired the ameboid morphology. This is characteristic of activated microglia/macrophages that has been reported to play an important role in dopamine terminal sprouting. In summary, our study shows that IS infusion of LGF stimulates the outgrowth of tyrosine hydroxylase-positive terminals in the striatum of 6-hydroxydopamine-treated rats. As apomorphine-induced rotational behavior was also reduced in these animals, we propose LGF as a novel factor that, when delivered to the striatum, may be useful in the treatment of Parkinson's disease. 相似文献
6.
Catabolite inactivation of the sugar transporters in Saccharomyces cerevisiae is inhibited by the presence of a nitrogen source 总被引:2,自引:0,他引:2
Saccharomyces cerevisiae uses glucose preferentially to any other carbon source and this preferential use is ensured by control mechanisms triggered by glucose. The consensus is that inactivation of sugar transporters other than glucose transporters is one of these mechanisms. This inactivation is called catabolite inactivation because of its apparent analogy with the catabolite inactivation of gluconeogenic enzymes. Recently, doubt has been cast on the role of the inactivation of the sugar transporters in controlling the use of glucose because this inactivation neither is specifically triggered by glucose nor specifically affects non-glucose sugar transporters. Based on the fact that this inactivation has been almost exclusively investigated using nitrogen-starved cells, it has been proposed that it might be due to the stimulation of the protein turnover that follows nitrogen starvation. The results obtained in this work support this possibility since they show that the presence of a nitrogen source in the medium strongly inhibited the inactivation. It is concluded that, in growing yeast cells, the contribution of the inactivation by glucose of the non-glucose sugar transporters to the preferential use of glucose is much lower than generally believed. 相似文献
7.
8.
Rafael Gonzalo-Gobernado Diana Reimers Antonio S. Herranz Juan Jos�� D��az-Gil Cristina Osuna Mar��a Jos�� Asensio Silvia Baena Macarena Rodr��guez-Serrano Eulalia Baz��n 《The journal of histochemistry and cytochemistry》2009,57(5):491-502
Neural stem cells with self-renewal and multilineage potential persist in the subventricular zone of the adult mammalian forebrain. These cells remain relatively quiescent but, under certain conditions, can be stimulated, giving rise to new neurons. Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and is useful for neuroregenerative therapies. The aim of this study was to investigate the potential neurogenic activity of LGF in the 6-hydroxydopamine rat model of Parkinson''s disease. Proliferation was significantly increased in the subventricular zone and denervated striatum of rats receiving ICV LGF infusions, and 25% of the proliferating cells were doublecortin-positive neurons. Doublecortin-positive cells with the morphology of migrating neuroblasts were also observed in the dorsal and ventral regions of the striatum of LGF-infused animals. Moreover, some newly generated cells were neuronal nuclei-positive mature neurons. LGF also stimulated microglia and induced astrogliosis, both phenomena associated with generation and migration of new neurons in the adult brain. In summary, our study shows that LGF stimulates neurogenesis when applied intraventricularly in 6-hydroxydopamine–lesioned rats. Considering that this factor also promotes neuronal migration into damaged tissue, we propose LGF as a novel factor useful for neuronal replacement in neurodegenerative diseases. (J Histochem Cytochem 57:491–502, 2009) 相似文献
9.
Contreras CE Donato Md Rivas MA Rodulfo H Mora R Batista ME Marcano N 《Memórias do Instituto Oswaldo Cruz》2011,106(2):123-129
In Venezuela, a total of 363,466 malaria cases were reported between 1999-2009. Several states are experiencing malaria epidemics, increasing the risk of vector and possibly transfusion transmission. We investigated the risk of transfusion transmission in blood banks from endemic and non-endemic areas of Venezuela by examining blood donations for evidence of malaria infection. For this, commercial kits were used to detect both malaria-specific antibodies (all species) and malaria antigen (Plasmodium falciparum only) in samples from Venezuelan blood donors (n = 762). All samples were further studied by microscopy and polymerase chain reaction (PCR). The antibody results showed that P. falciparum-infected patients had a lower sample/cut-off ratio than Plasmodium vivax-infected patients. Conversely, a higher ratio for antigen was observed among all P. falciparum-infected individuals. Sensitivity and specificity were higher for malarial antigens (100 and 99.8%) than for antibodies (82.2 and 97.4%). Antibody-positive donors were observed in Caracas, Ciudad Bolívar, Puerto Ayacucho and Cumaná, with prevalences of 1.02, 1.60, 3.23 and 3.63%, respectively. No PCR-positive samples were observed among the donors. However, our results show significant levels of seropositivity in blood donors, suggesting that more effective measures are required to ensure that transfusion transmission does not occur. 相似文献
10.
Esterina Pascale Christine Liu Eulalia Valle Karen Usdin Anthony V. Furano 《Journal of molecular evolution》1993,36(1):9-20
Summary All modern mammals contain a distinctive, highly repeated (⩾50,000 members) family of long interspersed repeated DNA called
the L1 (LINE 1) family. While the modern L1 families were derived from a common ancestor that predated the mammalian radiation
∼80 million years ago, most of the members of these families were generated within the last 5 million years. However, recently
we demonstrated that modern murine (Old World rats and mice) genomes share an older long interspersed repeated DNA family
that we called Lx. Here we report our analysis of the DNA sequence of Lx family members and the relationship of this family
to the modern L1 families in mouse and rat. The extent of DNA sequence divergence between Lx members indicates that the Lx
amplification occurred about 12 million years ago, around the time of the murine radiation. Parsimony analysis revealed that
Lx elements were ancestral to both the modern rat and mouse L1 families. However, we found that few if any of the evolutionary
intermediates between the Lx and the modern L1 families were extensively amplified. Because the modern L1 families have evolved
under selective pressure, the evolutionary intermediates must have been capable of replication. Therefore, replicationcompetent
L1 elements can reside in genomes without undergoing extensive amplification. We discuss the bearing of our findings on the
evolution of L1 DNA elements and the mammalian genome. 相似文献