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1.
Abstract: Possible roles of prostaglandins (PGs) in interleukin-1 (IL-1)-induced activation of noradrenergic neurons were examined by assessing norepinephrine (NE) turnover in the brain and peripheral organs of rats. An intraperitoneal injection of human recombinant IL-1β accelerated NE turnover in the hypothalamus, spleen, lung, diaphragm, and pancreas. A similar increase in NE turnover was also observed after intracerebroventricular injection of corticotropin-releasing hormone (CRH). Pretreatment with indomethacin (cyclooxygenase inhibitor) abolished the IL-1-induced, but not the CRH-induced, increase in hypothalamic and splenic NE turnover. To elucidate which eicosanoid-cyclooxygenase product(s) is responsible for accelerating NE turnover, PGD2, PGE2, PGF, U-46619 (stable thromboxane A2 analogue), or carbacyclin (stable prostacyclin analogue) was administered intracerebroventricularly. Among them, PGE2 was the only eicosanoid effective in increasing NE turnover in spleen, whereas PGD2 was effective in the hypothalamus. The stimulative effect of PGD2 was abolished by pretreatment with intracerebroventricular injection of a CRH antiserum. These results suggest that the action of IL-1 is mediated through PGD2 production to activate the noradrenergic neurons in the hypothalamus, and through PGE2 production to increase sympathetic nerve activity in spleen.  相似文献   

2.
Abstract: The myelin specific protein, P2, was localized immunocytochemically in electron micrographs of 4-day-old rat peripheral nerve by a preembedding technique. P2 staining was restricted to Schwann cells that had established a one-to-one relationship with an axon. P2 antiserum produced a diffuse staining throughout the entire cytosol of myelinating Schwann cells. In addition, the cytoplasmic side of Schwann cell plasma membranes and the membranes of cytoplasmic organelles that were exposed to cytosol were stained by P2 antiserum. This cytoplasmic localization of P2 protein is similar to that described for soluble or peripheral membrane proteins that are synthesized on free ribosomes. P2 antiserum stained the cytoplasmic side of Schwann cell membranes that formed single or multiple loose myelin spirals around an axon. In the region of the outer mesaxon, P2 antiserum stained the major dense line of compact myelin. These results demonstrate that P2 protein is located on the cytoplasmic side of compact myelin membranes and are consistent with biochemical studies demonstrating P2 to be a peripheral membrane protein.  相似文献   

3.
Abstract: In homogenates of rat cerebral neocortex prostaglandin D2 (PGD2) was found to be quantitatively the main PG biosynthesized by a cytosolic PGD synthetase from en-dogenously released arachidonic acid. Amounts of 628 ng/g wet weight were found after 30-min incubation periods compared with basal levels of 2.3 ng/g wet weight. In human cerebral cortex, whether obtained at biopsy or postmortem, only small amounts of PGD2 (4.5–11.7 ng/g wet weight/30 min) were formed. Furthermore, PGD2, added to homogenates of human biopsy temporal cortex, was converted efficiently into 9α,11β-PGF2 by a NADPH-dependent 11-ke-toreductase as has been reported in other human tissues (liver and lung). PGF was determined directly as the fl-butylbo-ronate derivative. It became clear that 9α,11β-PGF2 was formed in considerably greater amounts than PGF and that other metabolites are also formed. These results can account for the low amounts of PGD2 found in incubations of human brain tissue. The rat brain does not contain 11-ketoreductase activity. The present results indicate that the 9α, 11β-PGF2 must be considered along with other eicosanoids in pathophysiological situations in brain.  相似文献   

4.
5.
Abstract: Platelet-activating factor (PAF) may be a neuromodulator involved in neural cell differentiation, cerebral inflammation, and ischemia. The PAF receptor is a member of the G protein-coupled receptor superfamily. In the present study, we sought to define the specific G protein(s) that mediate PAF-stimulated phosphoinositide (PI) metabolism in an immortalized hippocampal cell line, HN33.11. PAF increased the production of 3H-labeled inositol phosphates (IPs) with EC50 values of 1.2–1.5 n M . The effect of PAF on 3H-IPs formation was completely blocked by the PAF antagonist BN 50739 at a concentration of 300 n M . Pertussis toxin pretreatment attenuated PAF-stimulated 3H-IPs production by 20–30% ( p < 0.05). Consistent with a role for Gi1/2 in this response, antiserum against Gαi1/2 blocked the response to a similar degree. Pretreatment of permeabilized cells with Gαq/11 antiserum attenuated the response by 70% ( p < 0.05), suggesting a role for Gq/11 in mediating the PAF response in this cell line. Stimulation with PAF increased [α-32P]-GTP binding to both Gαq and Gαi1/2 proteins. Moreover, specific [3H]PAF binding sites coprecipitated with Gαq and Gαi1/2 proteins. The results suggest that PAF-stimulated PI metabolism in HN33.11 cells is mediated by both Gq and Gi1/2 proteins.  相似文献   

6.
Abstract— The dialysableglycopeptide preparation recovered from the glycoproteins in cerebral gray matter of a case of the O-variant form of GM2 gangliosidosis contained four fold more N -acetylglucosamine and mannose than a similar preparation from normal gray matter. In the O-variant form of GM2 gangliosidosis, the enzymes β - N -acetylhexosaminidases A and B are missing. A three- and four-fold elevation, respectively, of N -acetylglucosamine and mannose in the dialysable glycopeptide preparation from a case of Tay-Sachs disease (B-variant form of GM2 gangliosidosis) was noted. The B-variant lacks hexosaminidase A but has ample supplies of hexosaminidase B. The brain level of glycosaminoglycans was not affected in the O- and B-variant forms of GM2 gangliosidosis.  相似文献   

7.
Abstract: Coated vesicles (CVs) isolated from bovine striatal tissue were examined to determine whether they are associated with dopamine signal systems consisting of dopamine D1 and D2 receptors, G proteins, and adenylate cyclase. Dopamine receptors in CVs were characterized by a dopamine D1 receptor antagonist, [3H]SCH 23390, and a dopamine D2 receptor antagonist, [3H]-spiroperidol. The bindings of both ligands were specifically saturable and reversible with a dissociation constant ( K D) of 0.65 and 0.5 n M , respectively. Dopaminergic antagonists and agonists inhibited the specific bindings of [3H]SCH 23390 and [3H]spiroperidol in a stereoselective and concentration-dependent manner with an appropriate rank order potency for dopamine D1 or D2 receptors. The regulations of the agonist binding by guanyl-5-ylimidodiphosphate were observed. ADP ribosylation of the CVs with [32P]NAD demonstrated predominant labeling of bands of Mr 47,000–52,000, 42,000–45,000, and 40,000-39,000, which corresponded to the known molecular weights of the α subunits of Gs and Gi proteins. The presence of α and β subunits of G proteins in the CVs was also confirmed by immunoblotting assay. Adenylate cyclase activity, which was stimulated by SKF 38393 and inhibited by dopamine D2 receptor agonists, was present in the CVs. These findings suggest that the dopamine D1 and D2 receptors in the CVs couple with adenylate cyclase via Gs/Gi protein.  相似文献   

8.
Abstract: The amyloid protein (βA4) is found in the CNS of patients with Alzheimer's disease; however, the pathogenic role of this protein is not known. In the present study, a peptide fragment of βA4βA4 25–35; Gly-Ser-Asn-Lys-Gly-Ala-Ile-Ile-Gly-Leu-Met-NH2), which contains the conserved C-terminal sequence of substance P (X-Gly-Leu-Met-NH2), and the neuropeptide substance P (SP) were examined for their ability to modulate nicotine-evoked secretion from cultured bovine adrenal chromaffin cells. Secretion of the released endogenous catecholamines was monitored by electrochemical detection after separation by HPLC. Secretion induced by 10−5 M nicotine was inhibited by SP and βA4 25–35. The IC50 of SP and βA4 25–35 was 3 × 10−6 and 3 × 10−5 M , respectively. SP and βA4 25–35 both protected against nicotinic receptor desensitization. However, βA4 25–35 was ∼ 10-fold less effective than SP in its protective effect. The present work shows that βA4 25–35 can mimic the modulatory actions of SP on the nicotinic response of cultured bovine chromaffin cells, i.e., inhibition of the nicotinic response and protection against nicotinic desensitization. These modulatory actions may be associated with changes in nicotinic receptor levels reported to occur in Alzheimer's disease.  相似文献   

9.
Influence of soil O2 and CO2 on root respiration for Agave deserti   总被引:5,自引:0,他引:5  
Respiration measured as CO2 efflux was determined at various soil O2 and CO2 concentrations for individual, attached roots of a succulent perennial from the Sonoran Desert, Agave deserti Engelm. The respiration rate increased with increasing O2 concentration up to about 16% O2 for established roots and 5% O2 for rain roots (fine branch roots on established roots induced by wetting of the soil) and then remained fairly constant up to 21% O2. When O2 was decreased from 21 to 0%, the respiration rates were similar to those obtained with increasing O2 concentration. The CO2 concentration in the root zone, which for the shallow-rooted A. deserti in the field was about 1 000 μl l-1, did not affect root respiration at concentrations up to 2 000 μl l-1, but higher concentrations reduced it, respiration being abolished at 20 000 μl l-1 (2%) CO2 for both established and rain roots. Upon lowering CO2 to 1 000 μl l-1 after exposure to concentrations up to 10000 μl l-1 CO2, inhibition of respiration was reversible. Uptake of the vital stain neutral red by root cortical cells was reduced to zero, indicating cell death, in about 4 h at 2% CO2, substantiating the detrimental effects of high soil CO2 concentrations on roots of A. deserti . This CO2 response may explain why roots of desert succulents tend to occur in porous, well-aerated soils.  相似文献   

10.
Abstract: H2O2 and free radical-mediated oxidative stresses have been implicated in mediating amyloid β(1–40) [Aβ(1–40)] neurotoxicity to cultured neurons. In this study, we confirm that addition of the H2O2-scavenging enzyme catalase protects neurons in culture against Aβ-mediated toxicity; however, it does so by a mechanism that does not involve its ability to scavenge H2O2. Aβ-mediated elevation in intracellular H2O2 production is suppressed by addition of a potent H2O2 scavenger without any significant neuroprotection. Three intracellular biochemical markers of H2O2-mediated oxidative stress were unchanged by Aβ treatment: (a) glyceraldehyde-3-phosphate dehydrogenase activity, (b) hexose monophosphate shunt activity, and (c) glucose oxidation via the tricarboxylic acid cycle. Ionspray mass spectra of Aβ in the incubation medium indicated that Aβ itself is an unlikely source of reactive oxygen species. In this study we demonstrate that intracellular ATP concentration is compromised during the first 24-h exposure of neurons to Aβ. Our results challenge a pivotal role for H2O2 generation in mediating Aβ toxicity, and we suggest that impairment of energy homeostasis may be a more significant early factor in the neurodegenerative process.  相似文献   

11.
Prostaglandin E2 Induces Interleukin-6 Synthesis in Human Astrocytoma Cells   总被引:1,自引:1,他引:0  
Abstract: Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD) and prion diseases. Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis, appear to be beneficial in the treatment of AD. To assess whether PGs are able to induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were measured in a human astrocytoma cell line after stimulation with different PGs. PGE1 and PGE2, but not PGD2 and PGF, led to a rapid and transient induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1β-induced IL-6 mRNA synthesis. These results are discussed with respect to the participation of PGs in neurodegenerative diseases (and its inhibition by NSAIDs) by affecting cytokine expression.  相似文献   

12.
The quantitative relationship between C2H2 reduction, H2 evolution and 15N2 fixation was investigated in excised root nodules from pea plants ( Pisum sativum L. cv. Bodil) grown under controlled conditions. The C2H2/N2 conversion factor varied from 3.31 to 5.12 between the 32nd and the 67th day after planting. After correction for H2 evolution in air, the factor (C2H2-H2)/N2 decreased to values near the theoretical value 3, or in one case to a value significantly ( P < 0.05) below 3. The proportion of the total electron flow through nitrogenase, which is not wasted in H2 production but used for N2 reduction, is often stated as the relative efficiency (1-H2/C2H2). This factor varied significantly ( P < 0.05) during the growth period. The actual allocation of electrons to H2 and N2, expressed as the H2/N2 ratio, was independent of plant age, however. This discrepancy and the observation that the (C2H2-H2)/N2 conversion factor tended to be lower than 3, suggests that the C2H2reduction assay underestimates the total electron flow through nitrogenase.  相似文献   

13.
Neuropeptide Y (NPY) and NPY receptors are widely distributed in the CNS, including the retina, but the role of NPY in the retina is largely unknown. The aim of this study was to investigate whether NPY modulates intracellular calcium concentration ([Ca2+]i) changes in retinal neurons and identify the NPY receptors involved. As NPY decreased the [Ca2+]i amplitudes evoked by 30 mM KCl in only 50% of neurons analyzed, we divided them in two populations: NPY-non-responsive neurons (Δ2/Δ1 ≥ 0.80) and NPY-responsive neurons (Δ2/Δ1 < 0.80), being the Δ2/Δ1 the ratio between the amplitude of [Ca2+]i increase evoked by the second (Δ2) and the first (Δ1) stimuli of KCl. The NPY Y1/Y5, Y4, and Y5 receptor agonists (100 nM), but not the Y2 receptor agonist (300 nM), inhibited the [Ca2+]i increase induced by KCl. In addition, the inhibitory effect of NPY on evoked-[Ca2+]i changes was reduced in the presence of the Y1 or the Y5 receptor antagonists. In conclusion, NPY inhibits KCl-evoked [Ca2+]i increase in retinal neurons through the activation of NPY Y1, Y4, and Y5 receptors. This effect may be viewed as a potential neuroprotective mechanism of NPY against retinal neurodegeneration.  相似文献   

14.
Abstract: The β4 and β10 thymosins are G-actin binding proteins that exhibit complex patterns of expression during rat cerebellar development. Their expression in vivo is initially high in immature granule cells and diminishes as they migrate and differentiate, ceasing altogether by postnatal day 21. Thymosin β4 is present in a subset of glia throughout postnatal development, and its synthesis is also induced in maturing Bergmann glia. In contrast, thymosin β10 is only present at very low levels in a very small subpopulation of glia in the adult cerebellum. To study the factors differentially regulating expression of the β-thymosins, we characterized their patterns of expression in primary cultures of rat cerebellum. Both β-thymosins were initially expressed in granule cells, although expression, especially of thymosin β4, was truncated compared with the in vivo time course. As in vivo, thymosin β4 was synthesized at much higher levels in astrocytes and microglia in cultures from postnatal cerebellum than was thymosin β10. Unlike in vivo, the latter was expressed in glia cultured from fetal cerebellum. The similarities between the in vivo and in vitro expression of the β-thymosins show that modulation of tissue culture conditions could be used to identify factors regulating β-thymosin expression in vivo. The differences would identify regulatory mechanisms that are not evident from the in vivo studies alone.  相似文献   

15.
The role of a recently identified K+ATP channel in preventing H2O2 formation was examined in isolated pea stem mitochondria. The succinate-dependent H2O2 formation was progressively inhibited, when mitochondria were resuspended in media containing increasing concentration of KCl (from 0.05 to 0.15  M ). This inhibition was linked to a partial dissipation of the transmembrane electrical potential (ΔΨ) induced by KCl. Conversely, the malate plus glutamate-dependent H2O2 formation was not influenced. The succinate-sustained H2O2 generation was also unaffected by nigericin (a H+/K+ exchanger), but completely prevented by valinomycin (a K+ ionophore). In addition, cyclosporin A (a K+ATP channel opener) inhibited this H2O2 formation, while ATP (an inhibitor of the channel opening) slightly increased it. The inhibitory effect of ATP was strongly stimulated in the presence of atractylate (an inhibitor of the adenine nucleotide translocase), thus suggesting that the receptor for ATP on the K+ channel faces the intermembrane space. Finally, the succinate-dependent H2O2 formation was partially prevented by phenylarsine oxide (a thiol oxidant).  相似文献   

16.
The hydrogen peroxide (H2O2) stress response in Enterococcus faecalis ATCC19433 was investigated. A 2·4 mmol l−1 H2O2 pretreatment conferred protection against a lethal concentration (45 mmol l−1) of this agent. The relatively high concentrations of H2O2 used for adaptation and challenge treatments in Ent. faecalis emphasised the strong resistance towards oxidative stress in this species. Various stresses (NaCl, heat, ethanol, acidity and alkalinity) induced weak or strong H2O2 cross-protection. This paper describes the involvement of protein synthesis in the active response to lethal dose of H2O2, in addition to the impressive enhancement of synthesis of five H2O2 stress proteins. Combined results suggest that these proteins might play an important role in the H2O2 tolerance response.  相似文献   

17.
The density dependence of plant responses to elevated CO2   总被引:1,自引:0,他引:1  
1 Stands of the annual Brassica kaber were grown at a range of six densities in both ambient and elevated CO2 environments, and measurements of shoot growth were made from seedling emergence through to reproduction.
2 Early in stand development (21 days following emergence), CO2 enhancement (β) for above-ground biomass was highly density-dependent, ranging from 1.41 at the lowest density (20 plants m−2) to 0.59 at the highest density (652 plants m−2).
3 As stands matured and total biomass exceeded a relatively low threshold level (<10.0 g m−2; c.  20% of final yield), the density-dependence of β disappeared. Above this shoot biomass threshold, β-values remained remarkably stable (β = 0.34) across a broad range of stand biomass, independent of a stand's initial density or age.
4 Average stand-level reproductive β-values at a final harvest were very similar to biomass values (β = 0.38) and, as with biomass values at later stages, showed no apparent density-dependence.
5 These results highlight the importance of considering density and the time-course of stand development simultaneously when assessing the potential for CO2-induced growth enhancements in plants.  相似文献   

18.
Nitrogen nutrition of C3 plants at elevated atmospheric CO2 concentrations   总被引:5,自引:0,他引:5  
The atmospheric CO2 concentration has risen from the preindustrial level of approximately 290 μl l−1 to more than 350 μl l−1 in 1993. The current rate of rise is such that concentrations of 420 μl l−1 are expected in the next 20 years. For C3 plants, higher CO2 levels favour the photosynthetic carbon reduction cycle over the photorespiratory cycle, resulting in higher rates of carbohydrate production and plant productivity. The change in balance between the two photosynthetic cycles appears to alter nitrogen and carbon metabolism in the leaf, possibly causing decreases in nitrogen concentrations in the leaf. This may result from increases in the concentration of storage carbohydrates of high molecular weight (soluble or insoluble) and/or changes in distribution of protein or other nitrogen containing compounds. Uptake of nitrogen may also be reduced at high CO2 due to lower transpiration rates. Decreases in foliar nitrogen levels have important implications for production of crops such as wheat, because fertilizer management is often based on leaf chemical analysis, using standards estimated when the CO2 levels were considerably lower. These standards will need to be re-evaluated as the CO2 concentration continues to rise. Lower levels of leaf nitrogen will also have implications for the quality of wheat grain produced, because it is likely that less nitrogen would be retranslocated during grain filling.  相似文献   

19.
Abstract: Circular dichroism (CD) was used to study the conformations of bovine nerve root P2 basic protein, its reduced and carboxymethylated derivative (RCM-P2), and its large cyanogen bromide fragment (CN1). Data in the far UV show that both the parent protein and RCM-P2 have conformations dominated by a large amount of β structure. However, the CN1 peptide appears to exist in a largely unordered conformation. Since CN1 lacks short (20 residue) amino- and carboxy-terminal segments of the P2 protein, the spectral data suggest that these regions are important for determining and/or maintaining folding of the P2 protein in aqueous solutions. The P2 protein was found to have a distinctive CD spectrum in the near UV. The characteristics of molar ellipticities indicate that the spectrum contains significant contributions from tyrosine residues, and that these contributions suggest different environments for the two tyrosines in P2 protein. Both environments depend on protein conformation, since CD side chain absorptions are lost when P2 protein is denatured with 5 M urea.  相似文献   

20.
Abstract: Using receptors expressed from mouse brain mRNA in Xenopus oocytes, we found that enhancement of type A γ-aminobutyric acid (GABAA) receptor-gated Cl channel response is a common action of structurally diverse anesthetics, suggesting that the GABAA receptor plays an important role in anesthesia. To determine if GABAA receptor subunit composition influences actions of anesthetics, we expressed subunit cRNAs in Xenopus oocytes and measured effects of enflurane on GABA-activated Cl currents. Potentiation of GABA-activated currents by enflurane was dependent on the composition of GABAA receptor protein subunits; the order of sensitivity was α1β1 > α1β1γ2s1β1γ2L > total mRNA. The results suggest that anesthetics with simple structures may act on the GABAA receptor protein complex to modulate the Cl channel activity and provide a molecular explanation for the synergistic clinical interactions between benzodiazepines and general anesthetics.  相似文献   

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