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31.
Gliadin fragments induce phenotypic and functional maturation of human dendritic cells 总被引:6,自引:0,他引:6
Palová-Jelínková L Rozková D Pecharová B Bártová J Sedivá A Tlaskalová-Hogenová H Spísek R Tucková L 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(10):7038-7045
Celiac disease is a chronic inflammatory disease developing in genetically predisposed individuals. Ingested gliadin, the triggering agent of the disease, can cross the epithelial barrier and elicit a harmful T cell-mediated immune response. Dendritic cells (DC) are supposed to play a pivotal role in shaping the immune response. The direction of the immune response toward immunity or tolerance depends on the stage of maturation and the functional properties of the DC. DC become fully functional APC upon maturation by various stimuli. We investigated the effect of a peptic digest of gliadin on the maturation of human monocyte-derived DC. Stimulation of cells with gliadin, in contrast with other tested food proteins, led to enhanced expression of maturation markers (CD80, CD83, CD86, and HLA-DR molecules) and increased secretion of chemokines and cytokines (mainly of IL-6, IL-8, IL-10, TNF-alpha, growth-related oncogene, MCP-1, MCP-2, macrophage-derived chemokine, and RANTES). Maturation was accompanied by a greater capacity to stimulate proliferation of allogeneic T cells and significantly reduced endocytic activity. Furthermore, gliadin-induced phosphorylation of members of three MAPK families (ERK1/2, JNK, and p38 MAPK) was demonstrated. The largest contribution of p38 MAPK was confirmed using its inhibitor SB203580, which markedly down-regulated the gliadin-triggered up-regulation of maturation markers and cytokine production. Gliadin treatment also resulted in increased NF-kappaB/DNA binding activity of p50 and p65 subunits. Taken together, gliadin peptides can contribute to overcoming the stage of unresponsiveness of immature DC by inducing phenotypic and functional DC maturation, resulting in more efficient processing and presentation of gliadin peptides to specific T lymphocytes. 相似文献
32.
Complete analyses of NMR data of oxytocin (OT) and 4 analogues, ([o-MePhe(2)]OT, [mMe-Phe(2)]OT, [m-OMePhe(2)]OT and [p-MePhe(2)]OT), are given. The same conformational behavior in solution on one hand and large differences in biological activities on the other hand indicate that the compounds adopt a "biologically active conformation" at the stage of interaction with the receptor when the character of the substituent and its position on the aromatic ring may play a role in hindering attaining the ideal complementarity of both interacting components. 相似文献
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Olga Dawidowska Adam Prahl Tomasz Wierzba Lukasz Nowakowski Wioleta Kowalczyk Jirina Slaninová Bernard Lammek 《Journal of peptide science》2005,11(7):436-439
It was previously reported that acylation of the N-terminus of several known B(2) antagonists with various types of bulky acyl groups consistently improved their antagonistic potency in the rat blood pressure assay. On the other hand, earlier results seem to suggest that the effects of acylation on the contractility of isolated rat uterus depend substantially on the chemical character of the acyl group, as it was observed that this modification may either change the range of antagonism or even transform it into agonism. Bearing all this in mind, three new analogues of bradykinin were designed by modifying the moderately potent B(2) antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe-Thi-Arg. New analogues were obtained by acylation of the N-terminus of the above peptide with succinic acid, 12-aminododecanoic acid and 4-aminobenzoic acid in order to confirm whether either the positive or the negative charge on the N-terminal end of the peptide is responsible for the transformation of activity. The activity of analogues was assessed on blood pressure and in uterotonic in vitro tests. The modifications proposed either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, the three substituents, depending on their chemical character, differently influenced the interaction with the rat uterine receptors. The results may be of value in the design of new B(2) agonists and antagonists. 相似文献
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Lenka Valkovicova Silvia Minarikova Vavrova Jozef Mravec Jozef Grones Jan Turna 《Antonie van Leeuwenhoek》2013,104(6):899-911
Gene cluster “ter” conferring high tellurite resistance has been identified in various pathogenic bacteria including Escherichia coli O157:H7. However, the precise mechanism as well as the molecular function of the respective gene products is unclear. Here we describe protein–protein association and localization analyses of four essential Ter proteins encoded by minimal resistance-conferring fragment (terBCDE) by means of recombinant expression. By using a two-plasmid complementation system we show that the overproduced single Ter proteins are not able to mediate tellurite resistance, but all Ter members play an irreplaceable role within the cluster. We identified several types of homotypic and heterotypic protein–protein associations among the Ter proteins by in vitro and in vivo pull-down assays and determined their cellular localization by cytosol/membrane fractionation. Our results strongly suggest that Ter proteins function involves their mutual association, which probably happens at the interface of the inner plasma membrane and the cytosol. 相似文献
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Anna Vavrova Hana Jansova Eliska Mackova Miloslav Machacek Pavlina Haskova Lucie Tichotova Martin Sterba Tomas Simunek 《PloS one》2013,8(10)
Anthracyclines (such as doxorubicin or daunorubicin) are among the most effective anticancer drugs, but their usefulness is hampered by the risk of irreversible cardiotoxicity. Dexrazoxane (ICRF-187) is the only clinically approved cardioprotective agent against anthracycline cardiotoxicity. Its activity has traditionally been attributed to the iron-chelating effects of its metabolite with subsequent protection from oxidative stress. However, dexrazoxane is also a catalytic inhibitor of topoisomerase II (TOP2). Therefore, we examined whether dexrazoxane and two other TOP2 catalytic inhibitors, namely sobuzoxane (MST-16) and merbarone, protect cardiomyocytes from anthracycline toxicity and assessed their effects on anthracycline antineoplastic efficacy. Dexrazoxane and two other TOP2 inhibitors protected isolated neonatal rat cardiomyocytes against toxicity induced by both doxorubicin and daunorubicin. However, none of the TOP2 inhibitors significantly protected cardiomyocytes in a model of hydrogen peroxide-induced oxidative injury. In contrast, the catalytic inhibitors did not compromise the antiproliferative effects of the anthracyclines in the HL-60 leukemic cell line; instead, synergistic interactions were mostly observed. Additionally, anthracycline-induced caspase activation was differentially modulated by the TOP2 inhibitors in cardiac and cancer cells. Whereas dexrazoxane was upon hydrolysis able to significantly chelate intracellular labile iron ions, no such effect was noted for either sobuzoxane or merbarone. In conclusion, our data indicate that dexrazoxane may protect cardiomyocytes via its catalytic TOP2 inhibitory activity rather than iron-chelation activity. The differential expression and/or regulation of TOP2 isoforms in cardiac and cancer cells by catalytic inhibitors may be responsible for the selective modulation of anthracycline action observed. 相似文献
38.
Sobolewski D Prahl A Derdowska I Kwiatkowska A Slaninová J Lammek B 《Protein and peptide letters》2007,14(3):213-217
Synthesis of thirteen new analogues of arginine vasopressin (AVP) has been described. Amino acid residues at positions 2 and 3 of AVP, [3-mercaptopropionic acid (Mpa)(1)]AVP (dAVP), [Mpa(1),d-Arg(8)]VP (dDAVP) and [Mpa(1),Val(4),d-Arg(8)]VP (dVDAVP) were replaced with one amino acid residue using sterically constrained non-proteinogenic amino acids, 4-aminobenzoic acid (Abz), cis-4-aminocyclohexanecarboxylic acid (ach) or its trans-isomer (Ach). In the case of a potent V(1a) antagonist, [1-mercaptocyclohexaneacetic acid (Cpa)(1)]AVP, only one similar analogue has been prepared by replacing positions 2 and 3 with Abz. Unfortunately, all new peptides were inactive in bioassays for the pressor, antidiuretic and uterotonic in vitro activities in the rat. 相似文献
39.
Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor,NU7441
Ales Tichy Kamila Durisova Barbora Salovska Jaroslav Pejchal Lenka Zarybnicka Jirina Vavrova Natalie A. Dye Zuzana Sinkorova 《Radiation and environmental biophysics》2014,53(1):83-92
We studied the effect of pre-incubation with NU7441, a specific inhibitor of DNA-dependent protein kinase (DNA-PK), on molecular mechanisms triggered by ionizing radiation (IR). The experimental design involved four groups of human T-lymphocyte leukaemic MOLT-4 cells: control, NU7441-treated (1 μM), IR-treated (1 Gy), and combination of NU7441 and IR. We used flow cytometry for apoptosis assessment, Western blotting and ELISA for detection of proteins involved in DNA repair signalling and epifluorescence microscopy for detection of IR-induced phosphorylation of histone H2A.X. We did not observe any major changes in the amount of DNA-PK subunits Ku70/80 caused by the combination of NU7441 and radiation. Their combination led to an increased phosphorylation of H2A.X, a hallmark of DNA damage. However, it did not prevent up-regulation of neither p53 (and its phosphorylation at Ser 15 and 392) nor p21. We observed a decrease in the levels of anti-apoptotic Mcl-1, cdc25A phosphatase, cleavage of PARP and a significant increase in apoptosis in the group treated with combination. In conclusion, the combination of NU7441 with IR caused increased phosphorylation of H2A.X early after irradiation and subsequent induction of apoptosis. It was efficient in MOLT-4 cells in 10× lower concentration than the inhibitor NU7026. NU7441 proved as a potent radio-sensitizing agent, and it might provide a platform for development of new radio-sensitizers in radiotherapy. 相似文献
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JJ Sohn AJ Schetter HG Yfantis LA Ridnour I Horikawa MA Khan AI Robles SP Hussain A Goto ED Bowman LJ Hofseth J Bartkova J Bartek GN Wogan DA Wink CC Harris 《PloS one》2012,7(9):e44156