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21.
Quinones may be toxic by a number of mechanisms. including arylation and oxidative stress caused by redox cycling. Using isolated hepatocytes, we have studied the cytotoxicity of four quinones. with differing abilities to arylate cellular nucleophiles and redox cycle. in relation to their effects on cellular pyridine nucleotides. High concentrations of menadione (redox cycles and arylates). 2-hydroxy-1,4-naphthoquinone (neither arylates nor redox cycles via a one electron reduction) 2.3-dimethoxy-1.4-naphthoquinone (a pure redox cycler) and p-benzoquinone (a pure arylator) caused an initial decrease in NAD+ and loss of viability, which was not prevented by 3-aminobenzamide. an inhibitor of poly(ADP-ribose)polymerase. In contrast. 3-aminobenzamide inhibited the loss of NAD' and viability caused by dimethyl sulphate so implicating poly(ADP-ribose)polymerase in its toxicity but not that of the quinones. Non-toxic concentrations of menadione. 2.3-dimethoxy-1.4-naphthoquinone and 2-hydroxy-1.4-naphthoquinone all caused markedly similar changes in cellular pyridine nucleotides. An initial decrease in NAD+ was accompanied by a small. transient increase in NADP+ and followed by a larger. prolonged increase in NADPH and total NADP+ + NADPH. Nucleotide changes were not observed with non-toxic concentrations of p-benzoquinone. Our findings suggest that a primary event in the response of the cell to redox cycling quinones is to bring about an interconversion of pyridine nucleotides. in an attempt to combat the effects of oxidative stress 相似文献
22.
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
23.
Production of hybrids, amphiploids and backcross progenies between a cold-tolerant wild species, Erucastrum abyssinicum and crop brassicas 总被引:1,自引:0,他引:1
G. U. Rao M. Lakshmikumaran K. R. Shivanna 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1996,92(6):786-790
Three intergeneric hybrids were produced between a cold-tolerant wild species, Erucastrum abyssinicum and three cultivated species of Brassica, B. juncea, B. carinata and B. oleracea, through ovary culture. The hybrids were characterized by morphology, cytology and DNA analysis. Amphiploidy was induced in all the F1 hybrids through colchicine treatment. Stable amphiploids and backcross progenies were obtained from two of the crosses, E. abyssinicum x B. juncea and E. abyssinicum x B. carinata. The amphiploid, E. abyssinicum x B. juncea was successfully used as a bridge species to produce hybrids with B. napus, B. campestris and B. nigra. These hybrids and backcross progenies provide useful genetic variability for the improvement of crop brassicas. 相似文献
24.
25.
Corticotropin-releasing hormone (CRH) has been shown to be a central mediator for most, if not all, stress-induced responses. Since stressful stimuli may decrease hypothalamic tuberoinfundibular and tuberohypophysial dopaminergic neuronal activities, we aimed to determine whether CRH is involved. Using central administration of various doses of ovine CRH (oCRH; 1, 3 and 10 µg/rat) into the lateral cerebroventricle of either male or female rats, the neurochemical changes in various parts of the central nervous system, including the hypothalamus, were determined by high-performance liquid chromatography at various times after the injection (30, 60, 120 and 240 min). The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG), two major metabolites of dopamine and norepinephrine, respectively, in discrete brain regions were used as indices for catecholaminergic neuron activity. Plasma corticosterone levels increased significantly after all doses of oCRH and at all time points studied. oCRH also exerted significant stimulatory effects on noradrenergic neuron terminals in the frontal cortex, and on dopaminergic neuron terminals in the nucleus accumbens, hypothalamic paraventricular and periventricular nuclei, and intermediate pituitary lobe. Dopaminergic neuron terminals in the median eminence and the neural lobe of the pituitary, however, were not affected. There was no major difference in the responses between male and female rats. We conclude that CRH has a differential effect on central catecholaminergic neurons. 相似文献
26.
27.
Physiological Elevations of Glucocorticoids Potentiate Glutamate Accumulation in the Hippocampus 总被引:7,自引:0,他引:7
Becky A. Stein-Behrens Walter J. Lin Robert M. Sapolsky 《Journal of neurochemistry》1994,63(2):596-602
Abstract: Glucocorticoids (GCs) are secreted during stress and can damage the hippocampus over the course of aging and impair the capacity of hippocampal neurons to survive excitotoxic insults. Using microdialysis, we have previously observed that GCs augment the extracellular accumulation of glutamate and aspartate in the hippocampus following kainic acid-induced seizures. In that study, adrenalectomized rats maintained on minimal GC concentrations were compared with those exposed to GCs elevated to near-pharmacological levels. We wished to gain insight into the physiological relevance of these observations. Thus, we have examined the effects of GCs over the normal physiological range on glutamate and aspartate profiles; this was done by implanting adrenalectomized rats with GC-secreting pellets, which produce stable and controllable circulating GC concentrations. We observe that incremental increases in GC concentrations cause incremental increases in glutamate accumulation before the kainic acid insult, as well as in the magnitude of the glutamate response to kainic acid. Elevating GC concentrations from the circadian trough to peak doubled cumulative glutamate accumulation, whereas a rise into the stress range caused a fourfold increase in accumulation. Similar, although smaller, effects also occurred with aspartate accumulation (as well as with taurine but not glutamine accumulation). These data show that the highly elevated GC concentrations that accompany neurological insults such as seizure or hypoxia-ischemia will greatly exacerbate the glutamate accumulation at that time. Furthermore, stress levels of GCs augmented glutamate accumulation even in the absence of an excitotoxic insult, perhaps explaining how sustained stress itself damages the hippocampus. Finally, even the moderately ?levated basal GC concentrations that typically occur in aged rats augmented glutamate accumulation, perhaps explaining how GCs damage the hippocampus over the course of normal aging. 相似文献
28.
José M. Lora Jésus de la Cruz Tahía Benítez Antonio Llobell José A. Pintor-Toro 《Molecular & general genetics : MGG》1994,242(4):461-466
A cDNA clone encoding a putative cell wall protein (Qid3) was isolated from a library prepared from chitin-induced mRNA in cultures of the mycoparasitic fungus Trichoderma harzianum. The predicted 14 kDa protein shows a potential signal peptide, several hydrophobic domains and certain motifs that are structurally similar to proline-rich and glycine-rich plant cell wall proteins. Expression of the qid3 gene is derepressed in the absence of glucose. When introduced in yeast, qid3 expression causes cell division arrest into cytokinesis and cell separation, probably due to its cell wall localization. 相似文献
29.
The oxidative stress response in Bacillus subtilis 总被引:9,自引:0,他引:9
Barbara C.A. Dowds 《FEMS microbiology letters》1994,124(3):255-263
Abstract Bacillus subtilis undergoes a typical bacterial stress response when exposed to low concentrations (0.1 mM) of hydrogen peroxide. Protection is thereby induced against otherwise lethal, challenge concentrations (10 mM) of this oxidant and a number of proteins are induced including the scavenging enzymes, catalase and alkyl hydroperoxide reductase, and a putative DNA binding and protecting protein. Induced protection against higher concentrations (10–30 mM) of hydrogen peroxide is eliminated in a catalase-deficient mutant. Both RecA and Spo0A influence the basal but not the induced resistance to hydrogen peroxide. A regulatory mutation has been characterized that affects the inducible phenotype and is constitutively resistant to high concentrations of hydrogen peroxide. This mutant constitutively overexpresses the proteins induced by hydrogen peroxide in the wild-type. The resistance of spores to hydrogen peroxide is partly attributable to binding of small acid soluble proteins by the spore DNA and partly to a second step which coincides with the depletion of the NADH pool, which may inhibit the generation of hydroxyl radicals from hydrogen peroxide. 相似文献
30.
《Animal : an international journal of animal bioscience》2023,17(4):100727
The aim of this study is built in two phases: to quantify the ability of novel milk metabolites to measure between-animal variability in response and recovery profiles to a short-term nutritional challenge, then to derive a resilience index from the relationship between these individual variations. At two different stages of lactation, sixteen lactating dairy goats were exposed to a 2-d underfeeding challenge. The first challenge was in late lactation, and the second was carried out on the same goats early in the following lactation. During the entire experiment period, samples were taken at each milking for milk metabolite measures. For each metabolite, the response profile of each goat was characterised using a piecewise model for describing the dynamic pattern of response and recovery profiles after the challenge relative to the start of the nutritional challenge. Cluster Analysis identified three types of response/recovery profiles per metabolite. Using cluster membership, multiple correspondence analyses (MCAs) were performed to further characterise response profile types across animals and metabolites. This MCA analysis identified three groups of animals. Further, discriminant path analysis was able to separate these groups of multivariate response/recovery profile type based on threshold levels of three milk metabolites: β-hydroxybutyrate, free glucose and uric acid. Further analyses were done to explore the possibility of developing an index of resilience from milk metabolite measures. Different types of performance response to short-term nutritional challenge can be distinguished using multivariate analyses of a panel of milk metabolites. 相似文献