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991.
Previous studies from this laboratory have shown that glutamine (Gln) uptake in a rat astrocytoma-derived C6 cell line shows characteristics similar with the uptake of a model ASC system substrate, threonine, whose pH-dependence and partial tolerance of Li(+) substitution for Na(+) resemble the ASCT2 variant of the system. In support of the previous findings, RT-PCR analysis revealed that C6 cells strongly express ASCT2 mRNA, but not at all GlnT mRNA or NAT2 mRNA, the A and N system variants specifically engaged in Gln transport in normal CNS. Other features of Gln transport in C6 cells indicating the involvement of ASCT2 system included its resistance to ouabain and stimulation of Gln efflux from the cells in the presence of excess Gln or cysteine (Cys), demonstrating that the system operates in the exchange mode. Replacement of NaCl in the incubation medium with isoosmotic sucrose did neither significantly affect the kinetics, nor any other major characteristics of Gln or Thr transport, including its pH-dependence, inhibition by ASCT system substrates or resistance to the model system A substrate-N-methylamino-isobutyric acid (MeAiB). 相似文献
992.
Nisio CD Brunetti L Esposito DL Recinella L Orlando G Michelotto B Vacca M 《Peptides》2003,24(8):1231-1236
Chromatin-derived acidic peptides (ACPs) have been shown to acutely modulate hypothalamic catecholamine release. To investigate whether this effect is mediated through membrane polysialylated neural-cell adhesion molecule (PSA-N-CAM), we pretreated rat hypothalamic synaptosomes with neuraminidase enzyme, which partially cleaves sialic acid residues from N-CAM, and perfused them with ACP-1 (Asp-Asp-Ser-Asp-Glu-Glu-Asn) or a more lipophilic derivative, ACP-2 ([Ala-Ile-Ser-Pro]-Asp-Asp-Ser-Asp-Glu-Glu-Asn). We have found that neuraminidase completely abolish the inhibitory effect of ACP-1 on dopamine release, while the inhibitory activity of ACP-1 on norepinephrine release is partially lost. On the other hand, ACP-2 inhibition of dopamine release is not modified by neuraminidase pretreatment. 相似文献
993.
Tatone C Delle Monache S Francione A Gioia L Barboni B Colonna R 《The International journal of developmental biology》2003,47(5):327-333
Protein kinase C (PKC), an enzyme playing a central role in signal transduction pathways, is activated in fertilized mouse eggs downstream of the fertilization Ca2+ signal, to regulate different aspects of egg activation. Given the presence of Ca2+-independent PKC isoforms within the egg, we investigated whether fertilization triggers PKC stimulation in mouse eggs by activating Ca2+-independent signalling pathways. An increase in PKC activity was detected as early as 10 min after the beginning of insemination, when about 90% of eggs had fused with sperm and the first Ca2+ rise was evident in most of the eggs. A similar level of activity was found 20 min later, when about 60% of eggs had resumed meiosis. When the Ca2+ increase was buffered by an intracellular Ca2+ chelating agent, PKC stimulation was not blocked but only slightly reduced. Confocal microscopy analysis revealed that the increase in PKC activity at fertilization coincided with the translocation of PKCdelta, a Ca2+-independent and diacylglycerol-dependent PKC isoform, to the meiotic spindle. When, in the absence of the Ca2+ signal, metaphase-anaphase transition was inhibited, PKCdelta moved to the meiotic spindle but still maintained a sustained cytoplasmic distribution. In summary, our results indicate that: 1) PKC activation is an early event of egg activation; 2) both Ca2+-dependent and Ca2+-independent pathways contribute to increased PKC activity at fertilization; 3) PKCdelta is one of the isoforms participating in this signalling process. 相似文献
994.
Nowicki M Lewczuk B Papiewska M Przybylska-Gornowicz B 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2003,41(3):141-147
The pineal functions are modulated by some neuropeptides including PHI and VIP. The presence of PHI-immunoreactive and VIP-immunoreactive nerve fibers in the pineal gland has been shown in several mammalian species. Both peptides influence the pineal serotonin N-acetyltransferase activity and melatonin synthesis. The aim of the present study was to examine the localization of PHI- and VIP-immunoreactive nerve fibers in the pig pineal gland. Four three-month old female pigs housed in natural light conditions, with free access to food and water, were used in the study. The pineals were fixed by perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer. An immunohistochemical ABC streptavidin-biotin-complex method was used for the demonstration of PHI and VIP. PHI- and VIP-immunopositive nerve fibers were found in the pineal gland as well as in the habenular and posterior commissural areas. In the pineal gland, the density of PHI-immunoreactive nerve fibers was considerably higher than that of the fibers containing VIP. PHI- and VIP-immunopositive nerve fibers were more abundant in the cortical than in the medullary part of the gland. The nerve fibers formed bundles in the pineal capsule, from where they penetrated to the connective tissue septa and formed a dense meshwork surrounding blood vessels. In the parenchyma, PHI- and VIP-immunoreactive nerve terminals created baskets around clusters of pinealocytes. No PHI- or VIP-immunopositive cells were found in the pig pineal gland. 相似文献
995.
Burdan F Madej B Radzikowska E Dudka J Korobowicz A Pasternak M Maciejewski R 《Acta physiologica Hungarica》2003,90(2):115-123
Cathepsins are lysosomal enzymes that are used a sensitive markers in various toxicological investigations. The purpose of this study was to evaluate and compare the influence of cimetidine and famotidine on the cerebral cortex, particularly on the activity of cortical cathepsin B, D and L in the frontal lobe of rat brain. The drugs were administered intraperitoneally, twice a day, for six weeks to male Wistar rats in two doses. The initial dose was 2.85 mg/kg for cimetidine and 0.285 mg/kg for famotidine. The second dose was 10 times higher. Control animals were injected with 0.9% NaCl. Half of the animals from each of the drug-treated and control groups were sacrificed on the 42nd day of the experiment. The remaining animals were raised for another 6 weeks without any xenobiotics, and sacrificed on the 84th day. The frontal lobe of the right cerebral hemisphere was taken for biochemical investigation. The activities of free and bound fractions of cathepsin B, D and L were evaluated spectrophotometrically in cortical homogenates. The activity of bound fraction of cathepsin D and L decreased significantly in animals exposed to the higher dose of cimetidine and sacrificed on the 42nd day. Also significant elevation of the free fraction of cathepsin L was noted in the same group of rats. Cathepsin activities were normalized during the next six weeks. No behavioural changes were noted among the observed animals. Unlike cimetidine, famotidine did not change profiles of the cerebral cathepsins. 相似文献
996.
Bernauer U Glatt H Heinrich-Hirsch B Liu Y Muckel E Vieth B Gundert-Remy U 《Alternatives to laboratory animals : ATLA》2003,31(1):21-30
A V79 Chinese hamster cell line was constructed for stable expression of mouse cytochrome P450 2e1 (Cyp2e1), as an addition to the existing cell battery consisting of cell lines stably expressing rat CYP2E1 and human CYP2E1 (V79 Cell Battery). The aim was to establish a cell battery that offers the in vitro possibility of investigating species-specific differences in the toxicity and metabolism of chemicals representing substrates for CYP2E1. The newly established cell line (V79m2E1) effectively expressed Cyp2e1 in the catalytically active form. The expression of catalytically active CYP2E1 in V79m2E1 cells was maintained over several months in culture, as demonstrated by Western Blotting and chlorzoxazone (CLX) 6-hydroxylase activity. The cells exhibited CLX 6-hydroxylase activity with a Km of 27.8 microM/l and Vmax of 40 pmol/mg protein/minute, compared with a Km of 28.2/28.6 microM/l and a Vmax of 130/60 pmol/mg protein/minute from V79r2E1/V79h2E1 cells. Furthermore, the CYP2E1-dependent mutagenicity of N-nitrosodimethylamine could be demonstrated in the V79m2E1 cells. Therefore, the new cell battery permits the interspecies comparison of CYP2E1-dependent toxicity and of metabolism of chemicals between humans and the two major rodent species--the rat and the mouse--that are usually used in classical toxicity studies. 相似文献
997.
Bélanger LF Roy S Tremblay M Brott B Steff AM Mourad W Hugo P Erikson R Charron J 《Molecular and cellular biology》2003,23(14):4778-4787
MEK is a dual-specificity kinase that activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase upon agonist binding to receptors. The ERK/MAP kinase cascade is involved in cell fate determination in many organisms. In mammals, this pathway is proposed to regulate cell growth and differentiation. Genetic studies have shown that although a single Mek gene is present in Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis, two Mek homologs, Mek1 and Mek2, are present in the mammalian cascade. The inactivation of the Mek1 gene leads to embryonic lethality and has revealed the unique role played by Mek1 during embryogenesis. To investigate the biological function of the second homolog, we have generated mice deficient in Mek2 function. Mek2 mutant mice are viable and fertile, and they do not present flagrant morphological alteration. Although several components of the ERK/MAP kinase cascade have been implicated in thymocyte development, no such involvement was observed for MEK2, which appears to be nonessential for thymocyte differentiation and T-cell-receptor-induced proliferation and apoptosis. Altogether, our findings demonstrate that MEK2 is not necessary for the normal development of the embryo and T-cell lineages, suggesting that the loss of MEK2 can be compensated for by MEK1. 相似文献
998.
The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization
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Scheper GC Parra JL Wilson M Van Kollenburg B Vertegaal AC Han ZG Proud CG 《Molecular and cellular biology》2003,23(16):5692-5705
The cap-binding eukaryotic initiation factor eIF4E is phosphorylated by the mitogen-activated protein (MAP) kinase-interacting kinases (Mnk's). Three forms of the Mnk's exist in human cells: Mnk1, Mnk2a, and Mnk2b. These last two are derived from the same gene by alternative splicing and differ only at their C termini. While Mnk2a contains a MAP kinase-binding site in this region, Mnk2b lacks such a sequence and is much less readily activated by MAP kinases in vitro. Expression of Mnk2b in mammalian cells leads to increased phosphorylation of eIF4E, showing that it acts as an eIF4E kinase in vivo. While Mnk2a is cytoplasmic, a substantial amount of Mnk2b is found in the nucleus. Both enzymes contain a stretch of basic residues in their N termini that plays a role in binding to eIF4G and functions as a nuclear localization signal. Binding of eIF4G or nuclear import appears to be regulated by the C terminus of Mnk2a. Furthermore, the MAP kinase-binding site of Mnk2a regulates nuclear entry. Within the nucleus, Mnk2b and certain variants of Mnk2a that are present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E. 相似文献
999.
Gene expression profile of butyrate-inhibited vascular smooth muscle cell proliferation 总被引:7,自引:0,他引:7
Ranganna K Yousefipour Z Yatsu FM Milton SG Hayes BE 《Molecular and cellular biochemistry》2003,254(1-2):21-36
Excessive proliferation of vascular smooth muscle cells (VSMCs) is a critical element in the development of several vascular pathologies, particularly in atherosclerosis and in restenosis due to angioplasty. We have shown that butyrate, a powerful antiproliferative agent, a strong promoter of cell differentiation and an inducer of apoptosis inhibits VSMC proliferation at physiological concentrations with no cytotoxicity. In the present study, we have used cDNA array technology to unravel the molecular basis of the antiproliferative effect of butyrate on VSMCs. To assess the involvement of gene expression in butyrate-inhibited VSMC proliferation, proliferating VSMCs were exposed to 5 mmol/1 butyrate 1 through 5 days after plating. Expression profiles of 1,176 genes representing different functional classes in untreated control and butyrate treated VSMCs were compared. A total of 111 genes exhibiting moderate (2.0–5.0 fold to strong (> 5.0 fold) differential expression were identified. Analysis of these genes indicates that butyrate treatment mainly alters the expression of four different functional classes of genes, which include: 43 genes implicated in cell growth and differentiation, 13 genes related to stress response, 11 genes associated with vascular function and 8 genes normally present in neuronal cells. Examination of differentially expressed cell growth and differentiation related genes indicate that butyrate-inhibited VSMC proliferation appears to involve down-regulation of genes that encode several positive regulators of cell growth and up-regulation of some negative regulators of growth or differentiation inducers. Some of the down-regulated genes include proliferating cell nuclear antigen (PCNA), retinoblastoma susceptibility related protein p130 (pRb), cell division control protein 2 homolog (cdc2), cyclin B1, cell division control protein 20 homolog (p55cdc), high mobility group (HMG) 1 and 2 and several others. Whereas the up-regulated genes include cyclin D1, p21WAF1, p14INK4B/p15INK5B, Clusterin, inhibitor of DNA binding 1 (ID1) and others. On the other hand, butyrate-responsive stress-related genes include some of the members of heat shock protein (HSP), glutathione-s-transferase (GST), and glutathione peroxidase (GSH-PXs) and cytochrome P450 (CYP) families. Additionally, several genes related to vascular and neuronal function are also responsive to butyrate treatment. Although involvement of genes that encode stress response, vascular and neuronal functional proteins in cell proliferation is not clear, cDNA expression array data appear to suggest that they may play a role in the regulation of cell proliferation. However, cDNA expression profiles indicate that butyrate-inhibited VSMC proliferation involves combined action of a proportionally large number of both positive and negative regulators of growth, which ultimately causes growth arrest of VSMCs. Furthermore, these butyrate-induced differential gene expression changes are not only consistent with the antiproliferative effect of butyrate but are also in agreement with the roles that these gene products play in cell proliferation. 相似文献
1000.
Albertini MC Accorsi A Citterio B Burattini S Piacentini MP Uguccioni F Piatti E 《Biochimie》2003,85(10):963-970
The effects of the exposure to a static magnetic field (sMF) of 0.3 +/- 0.03 T on the Fusarium culmorum were investigated in vitro. sMF inhibition of mycelia growth was accompanied by morphological and biochemical changes. Fungal conidia germination and cell viability were also reduced. We provide evidence of the influence of sMF on Ca(2+)-dependent signal transduction pathways involved in conidia germination. Perturbation of these pathways by adding different compounds (i.e. CaCl(2), phorbol 12-myristate 13-acetate, neomycin, EGTA, LiCl) to the medium, suggested that exposed conidia are unable to mobilise calcium from intracellular stores and that the hindered mechanism may be IP(3)-dependent. 相似文献