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51.
Inhibition of the mitochondrial Na+/Ca2+ exchanger (NCLX) by is protective in models of neuronal injury that involve disruption of intracellular Ca2+ homeostasis. However, the Ca2+ signaling pathways and stores underlying neuroprotection by that inhibitor are not well defined. In the present study, we analyzed how intracellular Ca2+ levels are modulated by CGP37157 (10 μM) during NMDA insults in primary cultures of rat cortical neurons. We initially assessed the presence of NCLX in mitochondria of cultured neurons by immunolabeling, and subsequently, we analyzed the effects of CGP37157 on neuronal Ca2+ homeostasis using cameleon-based mitochondrial Ca2+ and cytosolic Ca2+ ([Ca2+]i) live imaging. We observed that NCLX-driven mitochondrial Ca2+ exchange occurs in cortical neurons under basal conditions as CGP37157 induced a decrease in [Ca2]i concomitant with a Ca2+ accumulation inside the mitochondria. In turn, CGP37157 also inhibited mitochondrial Ca2+ efflux after the stimulation of acetylcholine receptors. In contrast, CGP37157 strongly prevented depolarization-induced [Ca2+]i increase by blocking voltage-gated Ca2+ channels (VGCCs), whereas it did not induce depletion of ER Ca2+ stores. Moreover, mitochondrial Ca2+ overload was reduced as a consequence of diminished Ca2+ entry through VGCCs. The decrease in cytosolic and mitochondrial Ca2+ overload by CGP37157 resulted in a reduction of excitotoxic mitochondrial damage, characterized here by a reduction in mitochondrial membrane depolarization, oxidative stress and calpain activation. In summary, our results provide evidence that during excitotoxicity CGP37157 modulates cytosolic and mitochondrial Ca2+ dynamics that leads to attenuation of NMDA-induced mitochondrial dysfunction and neuronal cell death by blocking VGCCs. CGP37157相似文献
52.
Phenotypic traits are expected to be more similar among closely related species than among species that diverged long ago (all else being equal). This pattern, known as phylogenetic niche conservatism, also applies to traits that are important to determine the niche of species. To test this hypothesis on ecological niches, we analysed isotopic data from 254 museum study skins from 12 of the 16 species of the bird genus Cinclodes and measured stable isotope ratios for four different elements: carbon, nitrogen, hydrogen and oxygen. We find that all traits, measured individually, or as a composite measurement, lack any phylogenetic signal, which in turn suggests a high level of lability in ecological niches. We compared these metrics to the measurements of morphological traits in the same genus and found that isotopic niches are uniquely evolutionarily labile compared to other traits. Our results suggest that, in Cinclodes, the realized niche evolves much faster than expected by the constraints of phylogenetic history and poses the question of whether this is a general pattern across the tree of life 相似文献
53.
Cintia González Blanco Eugenia Mato Matute Alberto de Leiva Hidalgo 《Endocrinología y nutrición》2012,59(7):452-458
Although papillary or follicular well-differentiated thyroid carcinoma usually has a good prognosis, a proportion of well-differentiated thyroid carcinomasshow a more aggressive behavior with local recurrence and metastases, either at diagnosis (in less than 5% of cases) or over time. Although there are several scoring systems to assess prognosis of well-differentiated thyroid carcinoma, mainly based on clinical and pathological data, there is currently no valid criterion to define an adequate, differential treatment for patients with low risk carcinomas as compared to those with more aggressive tumors. Identification of patients with a high risk at the time of diagnosis would be essential to develop new therapeutic strategies and to improve follow-up, and molecular biomarkers could be a highly useful tool for this purpose. 相似文献
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Del Caño Gontzal García Millán Luis Martínez Gerrikagoitia Inmaculada Sarasa Manuel Matute Carlos 《Brain Cell Biology》1999,28(6):455-468
The expression of ionotropic glutamate receptor subunits in the motoneuronal pools of the hypoglossal nucleus was studied using specific antibodies against subunits of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) subtypes. The highest numbers of intensely immunolabelled motoneurons were found in the dorsal tier and caudoventromedial part of the hypoglossal nucleus with all antibodies except that against the GluR1 AMPA subunit. Labelling for the GluR1 subunit was weak except for caudally located groups of motoneurons which innervate tongue muscles related to respiratory activity. By contrast, most motoneurons were intensely immunostained with antibodies against GluR2/3 and GluR4 subunits of the AMPA subtype. The low staining observed using an antibody specific for the GluR2 subunit (which prevents Ca2+-entry through AMPA channels) strongly suggests that AMPA receptors in hypoglossal motoneurons are Ca2+-permeable. Immunolabelling for the GluR5/6/7 kainate receptor subunits was found in many motoneuronal somata as well as in thin axon-like profiles and puncta that resembled synaptic boutons. Most motoneurons were intensely immunostained for the NMDA receptor subunit NR1. These results show that the hypoglossal nucleus contains five heterogeneous pools of motoneurons which innervate functionally defined groups of tongue muscles. The uneven expression of the different receptor subunits analysed here could reflect diverse phenotypic properties of hypoglossal motoneurons which might be expected to generate different patterns of motor responses under different physiological or pathological conditions. 相似文献
58.
Overactivation of ionotropic glutamate receptors induces a Ca2+ overload into the cytoplasm that leads neurons to excitotoxic death, a process that has been linked to several neurodegenerative disorders. While the role of mitochondria and its involvement in excitotoxicity have been widely studied, the contribution of endoplasmic reticulum (ER), another crucial intracellular store in maintaining Ca2+ homeostasis, is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine (RyR) and IP3 (IP3R) receptors to a neuronal in vitro model of excitotoxicity. NMDA induced a dose-dependent neuronal death, which was significantly decreased by ER-Ca2+ release inhibitors in cortical neurons as well as in organotypic slices. Furthermore, ryanodine and 2APB, RyR and IP3R inhibitors respectively, attenuated NMDA-triggered intracellular Ca2+ increase and oxidative stress, whereas 2APB reduced mitochondrial membrane depolarization and caspase-3 cleavage. Consistent with ER-Ca2+ homeostasis disruption, we observed that NMDA-induced ER stress, characterized here by eIF2α phosphorylation and over-expression of GRP chaperones which were regulated by ER-Ca2+ release inhibitors. These results demonstrate that Ca2+ release from ER contributes to neuronal death by both promoting mitochondrial dysfunction and inducing specific stress and apoptosis pathways during excitotoxicity. 相似文献
59.
We analyzed the distributional pattern of species and environmental gradients across inland water–land palm ecotones (morichals)
of the Orinoco lowlands to increase comprehension of the nature of ecotone heterogeneity. A total of 91 species (53 genera
and 45 families) with aboveground phytomass > 0.1 g dry mass were recorded. Detrented canonical correspondence analysis (DCCA)
indicated that vegetation phytomass was related strongly to soil properties, including gradients of silt (14.5–4.7%), exchangeable
Al (1.05–3.10 cmole kg−1), K (0.03–0.30 cmole kg−1), Na (0.01–0.08 cmole kg−1), Mg (0.03–0.54 cmole kg−1) concentrations, pH (3.7–5.0 units), and soil organic matter. Cluster analysis allowed the definition of four types of ecotones
on the basis of hydrogeomorphic processes. The first major group (1) encompassing the sites from Venezuelan lowlands (i.e.,
3V, 4V, 5V, 6V, and 7V) was related to less acidic soils with high organic matter content. The second group (II) from Eastern
Colombian llanos (i.e., sites 8C, 9C, 11C, 12C, 13C, 14C, and 15C) was located in acidic soils (3.9–4.5 units) with high Mg
concentration. The third group (III) (i.e., sites IV and 10C) was located in soils with high Na content, whereas the fourth
group (IV) (i.e., site 2V) was characterized by species growing in soils with low exchangeable aluminum. The results evidenced
the interactive role of valley constraint, landforms, hydrological regime, and soil feature in structuring the plant community.
Biogeographic and floristic considerations were also taken into account to explain differences in species composition. 相似文献
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