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Abstract: Reactive oxygen species have been implicated in neuronal injury associated with various neuropathological disorders. However, little is known regarding the relationship between antioxidant enzyme capacity and resultant toxicity. The antioxidant pathways of primary cerebrocortical cultures were directly examined using a novel technique that measures pentose phosphate pathway (PPP) activity, which is enzymatically coupled to glutathione peroxidase (GPx) detoxification of hydrogen peroxide (H2O2). PPP activity was quantified from data obtained by gas chromatography/mass spectrometry analysis of released labeled lactate following metabolic degradation of [1,6-13C2,6,6-2H2]glucose by cerebrocortical cultures. The antioxidant capacity of these cultures was systematically evaluated using H2O2, and the resultant toxicity was quantified by lactate dehydrogenase release. Exposure of primary mixed and purified astrocytic cultures to H2O2 caused stimulation of PPP activity in a concentration-dependent fashion from 0.25 to 22.2% and from 6.9 to 66.7% of glucose metabolized to lactate through the PPP, respectively. In the mixed cultures, chelation of iron before H2O2 exposure was protective and resulted in a correlation between PPP saturation and toxicity. Conversely, addition of iron, inhibition of GPx, or depletion of glutathione decreased H2O2-induced PPP stimulation and increased toxicity. These results implicate the Fenton reaction, reflect the pivotal role of GPx in H2O2 detoxification, and contribute to our understanding of the etiological role of free radicals in neuropathological conditions. 相似文献
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Sara Brosh Oded Sperling Esther Dantziger Yechezkel Sidi 《Journal of neurochemistry》1992,58(4):1485-1490
The metabolic fate of guanine and of guanine ribonucleotides (GuRNs) in cultured rat neurons was studied using labeled guanine. 8-Aminoguanosine (8-AGuo), an inhibitor of purine nucleoside phosphorylase, was used to clarify the pathways of GMP degradation, and mycophenolic acid, an inhibitor of IMP dehydrogenase, was used to assess the flux from IMP to GMP and, indirectly, the activity of the guanine nucleotide cycle (GMP----IMP----XMP----GMP). The main metabolic fate of guanine in the neurons was deamination to xanthine, but significant incorporation of guanine into GuRNs, at a rate of approximately 8.5-13.1% of that of the deamination, was also demonstrated. The turnover rate of GuRNs was fast (loss of 80% of the radioactivity of the prelabeled pool in 22 h), reflecting synthesis of nucleic acids (32.8% of the loss in radioactivity) and degradation to xanthine, guanine, hypoxanthine, guanosine, and inosine (49.3, 4.3, 4.1, 1.1, and 0.5% of the loss, respectively). Of the radioactivity in GuRNs, 7.9% was shifted to adenine nucleotides. The accumulation of label in xanthine indicates (in the absence of xanthine oxidase) that the main degradative pathway from GMP is that to xanthine through guanosine and guanine. The use of 8-AGuo confirmed this pathway but indicated the operation of an additional, relatively slower degradative pathway, that from GMP through IMP to inosine and hypoxanthine. Hypoxanthine was incorporated mainly into adenine nucleotide (91.5%), but a significant proportion (6%) was found in GuRNs.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Oded Haklai 《Ethnic and racial studies》2013,36(5):864-882
This article identifies the phenomenon of ethnic civil society activism as mobilization that seeks to empower an ethnic community and challenges the institutional order. The case of the Palestinian Arab minority in Israel is discussed and is used to reveal the conditions under which disaffected minorities pursue the path of ethnic civil society. The study finds that an analytical framework that stresses the mutability of state structures and changes in broader state-society relations provides a better explanation than existing theories of ethnic conflict. State-society characteristics conducive to this type of mobilization are a well-institutionalized state that can prevent deviation from the state's foundational rules and a counterbalanced dispersion of authority that limits regime capacity to control society. 相似文献
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Mountains provide an opportunity to examine changes in biodiversity across environmental gradients and areas of transition (ecotones). Mountain ecotones separate vegetation belts. Here, we aimed to examine whether transition areas for birds and butterflies spatially correspond with ecotones between three previously described altitudinal vegetation belts on Mt. Hermon, northern Israel. These include the Mediterranean Maquis, xero-montane open forest and Tragacanthic mountain steppe vegetation belts. We sampled the abundance of bird and butterfly species in 34 sampling locations along an elevational gradient between 500 and 2200 m. We applied wombling, a boundary-detection technique, which detects rapid changes in a continuous variable, in order to locate the transition areas for bird and butterfly communities and compare the location of these areas with the location of vegetation belts as described in earlier studies of Mt. Hermon. We found some correspondence between the areas of transition of both bird and butterfly communities and the ecotones between vegetation belts. For birds and butterflies, important transitions occurred at the lower vegetation ecotone between Mediterranean maquis and the xero-montane open forest vegetation belts, and between the xero-montane open forest and the mountain steppe Tragacanthic belts. While patterns of species turnover with elevation were similar for birds and butterflies, the change in species richness and diversity with elevation differed substantially between the two taxa. Birds and butterflies responded quite similarly to the elevational gradient and to the shift between vegetation belts in terms of species turnover rates. While the mechanisms generating these patterns may differ, the resulting areas of peak turnover in species show correspondence among three different taxa (plants, birds and butterflies). 相似文献
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Immune cells establish dynamic adhesive cell-cell interactions at a specific contact region, termed the immunological synapse (IS). Intriguing features of the IS are the formation of regions of plasma membrane fusion and the intercellular exchange of membrane fragments between the conjugated cells. It is not known whether upon IS formation, intact intracellular proteins can transfer from target cells to lymphocytes to allow the transmission of signals across cell boundaries. Here we show by both FACS and confocal microscopy that human lymphocytes acquire from the cells they scan the inner-membrane protein H-Ras, a G-protein vital for common lymphocyte functions and a prominent participant in human cancer. The transfer was cell contact-dependent and occurred in the context of cell-conjugate formation. Moreover, the acquisition of oncogenic H-RasG12V by natural killer (NK) and T lymphocytes had important biological functions in the adopting lymphocytes: the transferred H-RasG12V induced ERK phosphorylation, increased interferon-gamma and tumor necrosis factor-alpha secretion, enhanced lymphocyte proliferation, and augmented NK-mediated target cell killing. Our findings reveal a novel mode of cell-to-cell communication-allowing lymphocytes to extend the confines of their own proteome-which may moreover play an important role in natural tumor immunity. 相似文献