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Down's syndrome: abnormal neuromuscular junction in tongue of transgenic mice with elevated levels of human Cu/Zn-superoxide dismutase 总被引:17,自引:0,他引:17
To investigate the possible involvement of Cu/Zn-superoxide dismutase (CuZnSOD) gene dosage in the neuropathological symptoms of Down's syndrome, we analyzed the tongue muscle of transgenic mice that express elevated levels of human CuZnSOD. The tongue neuromuscular junctions (NMJ) in the transgenic animals exhibited significant pathological changes, namely, withdrawal and destruction of some terminal axons and the development of multiple small terminals. The ratio of terminal axon area to postsynaptic membrane decreased, and secondary folds were often complex and hyperplastic. The morphological changes in the transgenic NMJ were similar to those previously seen in muscles of aging mice and rats as well as in tongue muscle of patients with Down's syndrome. The findings suggest that CuZnSOD gene dosage is involved in the pathological abnormalities of tongue NMJ observed in Down's syndrome patients. 相似文献
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David Marr and others have hypothesized that the visual system processes complex scene information in stages, the first of which involves the detection of light intensity edges or zero-crossings (Marr, 1982). Ideal zero-crossing detector mechanisms have been described and modeled in terms of their possible physiological implementation (Marr and Hildreth, 1980; Poggio, 1983). We now present evidence of visual cortical receptive fields which resemble in spatial organizational terms the requirements of zero-crossing analysis. The linear and nonlinear summation within and between the receptive field subunits are described and compared with predicted processes. The relative subunit sizes and separations are analyzed in these terms. Our findings support the notion that receptive fields may correspond with zero-crossing filters rather than zero-crossing detector gates. 相似文献
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Boura-Halfon S Voliovitch H Feinstein R Paz K Zick Y 《The Journal of biological chemistry》2003,278(18):16397-16404
Internalization of the insulin receptor (IR) is a highly regulated multi-step process whose underlying molecular basis is not fully understood. Here we undertook to study the role of extracellular matrix (ECM) proteins in the modulation of IR internalization. Employing Chinese hamster ovary cells that overexpress IR (CHO-T cells), our results indicate that IR internalization proceeds unaffected even when Tyr phosphorylation of IR substrates, such as IRS-1, is impaired (e.g. in CHO-T cells overexpressing IRS-1 whose pleckstrin-homology domain has been deleted or in CHO-T cells that overexpress the PH/PTB domain of IRS-1). In contrast, IR internalization is affected by the context of the ECM proteins to which the cells adhere. Hence, IR internalization was inhibited 40-60% in CHO-T cells adherent onto galectin-8 (an ECM protein and an integrin ligand of the galectin family) when compared with cells adherent onto fibronectin, collagen, or laminin. Cells adherent to galectin-8 manifested a unique cytoskeletal organization, which involved formation of cortical actin and generation of F-actin microspikes that contrasted with the prominent stress-fibers formed when cells adhered to fibronectin. To better establish a role for actin filament organization in IR endocytosis, this process was assayed in CHO-T cells (adherent onto fibronectin), whose actin filaments were disrupted upon treatment with latrunculin B. Latrunculin B did not affect insulin-induced Tyr phosphorylation of IR or its ability to phosphorylate its substrates; still, a 30-50% reduction in the rate of IR internalization was observed in cells treated with latrunculin B. Treatment of cells with nocodazole, which disrupts formation of microtubules, did not affect IR internalization. These results indicate that proper actin, but not microtubular, organization is a critical requirement for IR internalization and suggest that integrin-mediated signaling pathways emitted upon cell adhesion to different extracellular matrices and the altered cytoskeletal organizations generated thereof affect the itinerary of the insulin receptor. 相似文献
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Diminished serotonin uptake in platelets of transgenic mice with increased Cu/Zn-superoxide dismutase activity. 总被引:7,自引:2,他引:5
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Reduced levels of the neurotransmitter serotonin in blood platelets is a clinical symptom characteristic of individuals with Down's syndrome. To investigate the possible involvement of the Cu/Zn-superoxide dismutase (CuZnSOD) gene, which resides at the Down locus on chromosome no. 21, in the etiology of that symptom, we examined blood platelets of transgenic mice harboring the human CuZnSOD gene. It was found that platelets of transgenic CuZnSOD animals, which overexpress the transgene, contain lower levels of serotonin than nontransgenic littermate mice, due to a reduced rate of uptake of the neurotransmitter by the dense granules of the platelets. We found that the pH gradient (delta pH) across the dense granule membrane, which is the main driving force for serotonin transport, was diminished in dense granules of transgenic-CuZnSOD. Furthermore, a significantly lower than normal serotonin accumulation rate was also detected in dense granules isolated from blood platelets of Down's syndrome individuals. These findings suggest that CuZnSOD gene dosage is affecting the dense granule transport system and is thereby involved in the depressed level of blood serotonin found in patients born with Down's syndrome. 相似文献
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Response of antioxidative enzymes to nickel and cadmium stress in hyperaccumulator plants of the genus Alyssum 总被引:10,自引:0,他引:10
The term 'phytoremediation' is used to describe the clean-up of heavy metals from contaminated soils by plants. In this study, we examined Alyssum argenteum and Alyssum maritimum for their ability to accumulate Cd2+ . We also exemined Ni2+ accumulation by A. maritimum with comparison with the known Ni-hyperaccumulator A. argenteum , in a hydroponic system. Both species were tolerant to low levels of Cd2+ , and accumulated high quantities under the experimental conditions. Only very low levels of Ni2+ were found in the shoot of A. maritimum , defining it as a non-hyperaccumulator. The role of the antioxidative enzyme system was investigated in relation to Ni2+ and Cd2+ stress. In both species, superoxide dismutase (SOD) activity was elevated at high Cd2+ concentrations, while ascorbate peroxidase (APX) activity remained unchanged and glutathione reductase (GR) activity was reduced. In the presence of Ni2+ , A. maritimum exhibited a typical antioxidative defense mechanism, as evidenced by the elevated activities of all three enzymes tested. A. argenteum exhibited a different enzyme response pattern, with a significant reduction in SOD activity, and elevated APX and GR activities only at the highest Ni2+ concentration. 相似文献
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Agricultural crops worldwide suffer from a vast array of fungal diseases which cause severe yield losses. Upon interaction
with a pathogen, plants initiate a complex network of defense mechanisms, among which is a dramatic increase in chitinase
activity. Chitinases are capable of hydrolyzing chitin-containing fungal cell walls and are therefore thought to play a major
role in the plant’s response. One of the strategies to increase plant tolerance to fungal pathogens is the constitutive
overexpression of proteins involved in plant-defense mechanisms. The level of protection observed in transgenic plants harboring
heterologous chitinase genes varies, depending on the particular combination of enzyme, plant and pathogen tested. Nevertheless,
most of these transgenic plants exhibit increased tolerance to fungal diseases relative to their non-transgenic counterparts.
The combined expression of chitinases with other plant-defense proteins such as glucanases and ribosome-inactivating proteins
further enhances the plant’s resistance to fungal attack.
Received 29 January 1997/ Accepted in revised form 01 July 1997 相似文献
10.
Degradation of Myogenic Transcription Factor MyoD by the Ubiquitin Pathway In Vivo and In Vitro: Regulation by Specific DNA Binding
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