Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks

Abstract: The pineal hormone melatonin has been shown to directly scavenge free radicals and to stimulate, in the mammalian brain, at least one enzyme, glutathione peroxidase, which reduces free radical generation. In the present studies, we examined the effect of melatonin on glutathione peroxidase activity in several tissues of an avian species. Melatonin (500 μg/kg), when injected into chicks, increased glutathione peroxidase activity within 90 min in every tissue examined. Tissue melatonin levels, measured by radioimmunoassay, also increased following its peripheral administration. Depending on the tissue, the measured increases in melatonin varied from 75% to 1,300% over the control values. The melatonin-induced increases in glutathione peroxidase activity varied with the tissue and were between 22% and 134%. These percentage increases in glutathione peroxidase activity were directly correlated with tissue melatonin content. These results suggest that melatonin induces the activity of the detoxifying enzyme, glutathione peroxidase, in several tissues in the chick. The findings also suggest that melatonin would reduce the generation of highly toxic hydroxyl radicals by metabolizing its precursor, hydrogen peroxide. Because of this ability to stimulate glutathione peroxidase activity, melatonin should be considered as a component of the antioxidative defense system in this avian species.     

Synthesis and Activity of the Glutathione Analogue γ-(L-γ-Oxaglutamyl)-L-cysteinyl-glycine

An efficient synthesis of the backbone modified glutathione analogue γ-(L-γ-oxaglutamyl)-L-cysteinyl-glycine ( 7 ), characterized by the presence of an urethane O-CO-NH linkage replacing the γ-glutamylic CH₂CO-NH fragment is described. The new analogue has been fully characterized by ¹H- and ¹³C-NMR, and FAB-MS. Compound 7 was tested for inhibition of γ-glutamyl-transferase activity and was found to be a non-competitive inhibitor of hog kidney γ-glutamyltransferase (EC 2.3.2.2).     

Age-dependent effects of t -BuOOH on glutathione disulfide reductase, glutathione peroxidase, and malondialdehyde in the brain

Intracerebroventriculart-butyl hydroperoxide has been reported to induce damage to many types of brain cells.t-Butyl hydroperoxide administration increases glutathione disulfide levels and decreases levels of glutathione. Young adult mice may be more protected fromt-butyl hydroperoxide than mature mice due to their higher glutathione levels, even after the adminstration oft-butyl hydroperoxide. This leads to our current study, investigating glutathione peroxidase and glutathione disulfide reductase in 2-mo-old and 8-mo-old mice. Furthermore, malondialdehyde levels were measured with the thiobarbituric acid assay and compared between the two age groups. Mature mice detoxify glutathione disulfide less readily than young adult mice. Glutathione disulfide reductase activity increases in young adult mice aftert-butyl hydroperoxide administration, but not in mature mice. Glutathione peroxidase activity is significantly lower in 8-mo-old than 2-mo-old mouse striatum aftert-butyl hydroperoxide administration. Furthermore, malondialdehyde levels in the 8-mo-old striatum increase significantly 20 min aftert-butyl hydroperoxide administration. This suggests that age plays a factor in protective mechanisms that are involved in oxidative stress in the brain.     

重组日本血吸虫谷胱甘肽S-转移酶的纯化

[目的] 原核表达并纯化重组日本血吸虫谷胱甘肽S转移酶．[方法] 将表达载体pGEX-5X-1转化至大肠杆菌BL21中，用异丙基硫代-β-D-半乳糖苷诱导，以十二烷基硫酸钠．聚丙烯酰胺凝胶电泳进行分析，产物用谷胱甘肽琼脂糖树脂纯化．[结果] 获得了纯化的谷胱甘肽S转移酶。     

地血香乙醇提取物对小鼠肝细胞中抗氧化酶活性的影响

本文报道地血香乙醇提取物和其主要成分Kadsurin对小鼠肝细胞中抗氧化酶活性的影响。地血香和Kadsurin能够明显增加肝细胞中超氧物歧化酶和过氧化氢酶的活性，而对谷胱甘肽过氧化物酶活性的影响无统计学意义。     

Effect of naturally occurring phenolic acids on the expression of glutathione S-transferase isozymes in the rat.

Naturally occurring plant phenols, protocatechuic and tannic acids, have been reported to be inhibitors of chemical mutagenesis and carcinogenesis in experimental models. Our previous studies, have shown that these compounds modulate the activity of phases 1 and 2 enzymes in rodents. The aim of the present study was to investigate whether these compounds affect protein levels of rat hepatic and renal glutathione S-transferase (GST) isozymes. Male Wistar rats were treated intraperitoneally with protocatechuic or tannic acid at 50 mg/kg body weight five times during 14 days. 3-Methylcholanthrene (MC) was administered at 20 mg/kg body weight on day 13 (the last treatment with phenolic compounds) and on day 14. Tissues were obtained from rats terminated 24 h after the last treatment. Western blot analysis with specific antibodies showed significant differences in the effect of the phenolic compounds in the liver and kidney. In the liver, protocatechuic acid significantly increased the constitutive GSTmicro, while tannic acid reduced the GSTalpha protein level by 60%. Both plant phenols decreased all classes of constitutive GST isozymes in the kidney including GSTpi, and also the MC-induced GSTalpha and/or pi protein levels. These results, as well as our previous reports, suggest that protocatechuic and tannic acids interfere with the pathways related to xenobiotic toxicities and carcinogenesis. This effect may be important for chemoprotective activity of these plant phenols.     

Postnatal development of corticotectal neurons in the kitten striate cortex: a quantitative study with the horseradish peroxidase technique

Postnatal development of striate cortical neurons projecting to the superior colliculus (SC) was studied in cats, ranging in age from newborn to adult, by injection of horseradish peroxidase (HRP) into the SC. At birth HRP-labelled cells were widely distributed throughout the cortex between the splenial and suprasylvian sulci, although a very rough topographic correspondence seemed to exist between the striate cortex and SC. The labelled cells were confined to layer V of the cortex, as in the adult. They were very densely packed and their somas were already pyramidal in shape although very slender. During the third to eighth days, apical dendrites of a substantial number of cells, mostly located in the upper bank of the splenial sulcus, were filled with HRP up to layer I and their somas were larger than those of cells located near the crown of the lateral and postlateral gyri. At the eighth day and thereafter, the distribution of the labelled cells across the visual cortex was not so widespread as that seen in the newborn kittens. The dendritic arborization pattern of labelled cells became nearly adultlike at the four week, and its full maturation was seen at the eighth week. A quantitative analysis of the cross-sectional areas of the cells and their packing density in layer V of the cortex revealed that (1) the size of cells increased very rapidly during the second week and became almost adultlike at the fifth week; (2) the density of cells reduced dramatically during the second week and thereafter at a low rate until the eighth week; and (3) the ratio of the labelled to unlabelled cells in layer V decreased remarkably also during the second week. These results suggest that an elimination of axon collaterals of corticotectal cells or their death may take place mostly during the second week of age, when eye-opening occurs in kittens. By comparison with previous data on functional development of the SC, it is also suggested that the maturation of visual response properties of SC neurons may depend on postnatal development of corticotectal cells.     

Single thalamic neurons which project to both the rostral cortex and caudate nucleus studied with the fluorescent double labeling method

After injections of fast blue into the rostral cortex and Evans blue into the caudate nucleus in cats, doubly labeled neurons were present in the ventral anterior, ventral lateral, rhomboid, and mediodorsal thalamic nuclei. Doubly labeled cells were also found in most members of the intralaminar group, including the central medial, paracentral, central lateral, and parafascicular nuclei. Although the centromedian nucleus contained large numbers of cells labeled with Evans blue which project to the caudate nucleus, and a few fast-blue labeled cells which projected to the cortex, doubly labeled neurons were absent from this posterior intralaminar nucleus in this study.     

Neocortical projections of the suprageniculate and posterior thalamic nuclei in the marsupial brush-tailed possum,Trichosurus vulpecula(phalangeridae), with a comparative commentary on the organization of the posterior thalamus in marsupial and placental mammals

Axonal transport methods were used to determine the extent and organisation of neocortical projections from the Suprageniculate (SG) and posterior (PO) thalamic nuclei in the brush-tailed possum. Our findings show that SG projects extensively to the auditory cortex, overlapping the cortical projection field of the modial geniculatc nucleus, and to the immediately neighbouring association cortex. Though the input relationships of SG appear similar to those reported for other mammals, placental and marsupial, a strong SG projection to auditory cortex has not been reported previously. Neocortical relationships of PO are characterised by an orderly point-to-point projection to all but the most rostral parts of the motor-somaesthetic cortex. There is also a substantial projection to the entire posterior parietal association cortex. The PO-neocortex projection is reciprocally organised. The PO-neocortical projection in the possum is similar to that reported in the Virginia opossum, rat, and several other mammals. There is a major difference in organisation in comparison with certain monkeys where the PO projection is much more restricted and does not involve the motor and som-aesthetic cortex. We conclude that PO is similarly organised in many, though not all, mammals, including the marsupials, rodents, insectivores, and prosimian primates. The possum SG, on the other hand, is clearly distinct from other mammals in its extensive projection to auditory cortex, though we cannot say at present whether this a general property of marsupial mammals or a peculiarity restricted to this species and possibly its close relatives.     

Acceleration of the regeneration of the crushed hypoglossal nerve by testosterone

The effect of testosterone propionate (TP) on regeneration of the crushed hypoglossal nerve was studied in young adult rats. The TP treatment promoted axonal outgrowth as measured by an increase in the proportion of hypoglossal neurons labeled by retrograde transport of horseradish peroxidase injected into the tongue at selected postlesion periods compared with that in controls. The result indicated that TP exerts its effect on regeneration primarily by increasing the metabolic activity in hormone target neurons. The somatotopic organization of the hypoglossal nucleus and its projection into the major nerve branches were unaltered subsequent to crush injury. The maintenance of specificity was attributed to the intact perineurial and endoneurial sheaths which guided regenerating fibers to their original targets.