排序方式: 共有22条查询结果,搜索用时 15 毫秒
1.
Zhang Z Vezza R Plappert T McNamara P Lawson JA Austin S Praticò D Sutton MS FitzGerald GA 《Circulation research》2003,92(10):1153-1161
Gh is a GTP binding protein that couples to the thromboxane receptor (TP), but also functions as tissue transglutaminase II (tTG). A transgenic mouse model was generated in which Gh was overexpressed (GhOE) in ventricular myocytes under the control of the alpha-myosin heavy chain promoter. Heart rate was elevated and both blood pressure and left ventricular ejection fraction were depressed in GhOEs. Left ventricular mass was increased, consistent with genetic and ultrastructural evidence of hypertrophy. Fibrosis and apoptosis were also augmented. Survival declined disproportionately in older GhOEs. Cardiomyocyte expression of COX-2, thromboxane synthase (TxS), and the receptors for TxA2 (the TP), PGF2alpha (the FP), and PGI2 (the IP) were upregulated and urinary 8,12-iso-iPF2alpha-VI,2,3-dinor-6-keto-PGF1alpha and 2,3-dinor-thromboxane B2 were increased in GhOEs, reflecting increased lipid peroxidation and cyclooxygenase (COX) activation. Selective COX-2 inhibition, TP antagonism, and suppression of lipid peroxidation each rescued the cardiac phenotype. Infusion of an FP agonist exacerbated the phenotype, whereas administration of an IP agonist improved cardiac function. Directed cardiac overexpression of Gh/tTG causes both TG activation and increased TP/Gh-dependent signaling. The COX-2-dependent increase in TxA2 generation augments cardiac hypertrophy, whereas formation of PGI2 by the same isozyme ameliorates the phenotype. Oxidant stress may contribute, via regulation of COX-2 expression and/or ligation of the TP and the FP by isoprostanes. Gh/tTG activation regulates expression of COX-2 and its products may differentially modulate cardiomyocyte commitment to cell death or survival. 相似文献
2.
Prostaglandin E2 (PGE2) is produced by activated platelets and by several other cells, including capillary endothelial cells. PGE2 exerts a dual effect on platelet aggregation: inhibitory, at high, supraphysiologic concentrations, and potentiating, at low concentrations. No information exists on the biochemical mechanisms through which PGE2 exerts its proaggregatory effect on human platelets. We have evaluated the activity of PGE2 on human platelets and have analyzed the second messenger pathways involved. PGE2 (5 to 500 nmol/L) significantly enhanced aggregation induced by subthreshold concentrations of U46619, thrombin, adenosine diphosphate (ADP), and phorbol 12-myristate 13-acetate (PMA) without simultaneously increasing calcium transients. At a high concentration (50 mumol/L), PGE2 inhibited both aggregation and calcium movements. PGE2 (5 to 500 nmol/L) significantly enhanced secretion of beta-thromboglobulin (beta TG) and adenosine triphosphate from U46619- and ADP-stimulated platelets, but it did not affect platelet shape change. PGE2 also increased the binding of radiolabeled fibrinogen to the platelet surface and increased the phosphorylation of the 47-kD protein in 32P- labeled platelets stimulated with subthreshold doses of U46619. Finally, the amplification of U46619-induced aggregation by PGE2 (500 nmol/L) was abolished by four different protein kinase C (PKC) inhibitors (calphostin C, staurosporine, H7, and TMB8). Our results suggest that PGE2 exerts its facilitating activity on agonist-induced platelet activation by priming PKC to activation by other agonists. PGE2 potentiates platelet activation at concentrations produced by activated platelets and may thus be of pathophysiologic relevance. 相似文献
3.
Prostaglandin (PG) F(2alpha) may act on its G protein-coupled receptor (FP) or be imported intracellularly via a transporter, which has high affinity for PGF(2alpha) and PGE(2), but not prostacyclin (PGI(2)). In cells overexpressing the epitope-tagged FP together with the human prostaglandin transporter (hPGT), stimulation of the FP with PGF(2alpha) (1 nM-1 microM), or the less potent FP agonist, the isoprostane 8,12-iso-iPF(2alpha)-III, inhibited prostaglandin uptake via the hPGT. This effect was abolished by pretreatment of the cells with cholera toxin, but not with pertussis toxin. Furthermore, two dominant negative constructs directed against Galpha(s) partially blocked FP-mediated regulation of hPGT function, also suggesting Galpha(s) involvement in this phenomenon. Surprisingly, neither an activator (dibutyryl cyclic AMP) nor an inhibitor (H89) of cyclic AMP-dependent protein kinase had any effect on FP-mediated inhibition of hPGT activity. Furthermore, although PGF(2alpha) increases intracellular cyclic AMP via Galpha(s) activation, it does not induce phosphorylation of the transporter, excluding a role of cyclic AMP-dependent protein kinase in hPGT regulation. Activation of the PGI(2) receptor, which is also coupled to Galpha(s), does not regulate hPGT activity, despite markedly augmenting adenylate cyclase activation. In conclusion, activation of the FP reduces intracellular import of prostaglandins for metabolic inactivation, increasing prostanoid availability for membrane receptor activation. This effect seems to be mediated via Galpha(s), independent of adenylate cyclase and cyclic AMP-dependent protein kinase activation. 相似文献
4.
The number and expression of some of the large ribosomal RNA (rRNA) gene classes present in the human malaria parasite Plasmodium falciparum was determined. Southern blot analyses, using the 5.8S rRNA coding region as a marker, indicate that the P. falciparum genome contains at least 5 distinct subclasses of large rRNA genes. Dideoxy sequencing of the 5.8S rRNA domain and Northern blot analyses demonstrate that only one subclass is transcribed during the parasite's asexual erythrocytic life cycle. 相似文献
5.
The ability of arenaviruses to form recombinant viruses by viral RNA segment reassortment has been investigated using a cloned, high-temperature adapted strain of prototype Pichinde virus (PIC), and a cloned, alternate Pichinde virus topotype named Pichinde Munchique (designated MUC). The oligonucleotide fingerprints of the large and small viral RNA segments of the two viruses can be easily distinguished. The virion RNA species of cloned wild-type progeny viruses recovered from dual wild-type PIC and MUC coinfections of BHK-21 cells have been analyzed by oligonucleotide fingerprinting. Other than PIC and MUC genotypes, progeny virus clones were found with PIC/MUC (large/small) RNA segment genotypes, indicating that these recombinant arenaviruses were formed by RNA segment reassortment. Dual infections of BHK-21 cells with a temperature-sensitive (ts), conditional lethal, mutant of MUC and the Group I ts mutants of PIC (but not the PIC Group II ts mutants), have yielded wild-type progeny viruses at high frequency. Genotype analysis of one of these recombinant progeny showed that it had a PIC/MUC genotype. This result indicated that the Group I mutants of PIC have a defective small viral RNA segment, and that the MUC ts mutant (and probably the PIC Group II ts mutants) has a defective large viral RNA segment. Plaque size analyses of the parental wild-type and reassortment viruses have shown that the plaque size of the reassortants was determined by the large viral RNA segment. Tryptic peptide analyses of the nucleocapsid (N) polypeptide of the PIC/MUC recombinant by comparison to similar analyses for PIC and MUC indicate that the recombinant has a MUC N polypeptide, i.e., that the viral S RNA codes for N polypeptide. 相似文献
6.
D Shippen-Lentz R Ray J G Scaife G Langsley A C Vezza 《Molecular and biochemical parasitology》1987,22(2-3):223-231
The 5.8S and 5S rRNA components from the FCR-3/The Gambia strain of Plasmodium falciparum have been identified and the complete nucleotide sequence of a 5.8S ribosomal RNA gene determined. Unlike the 5S rRNA species, the 5.8S is a single homogeneous population of molecules of 157 nucleotides. Comparison of its nucleotide sequence with previously reported 5.8S rRNA sequences indicates that it is homologous to these molecules, but distantly related to them. The sequence of the 5.8S rRNA coding region from the pfrib-2 recombinant of the HG13 Gambian isolate of P. falciparum is identical. 相似文献
7.
C. Cordova A. Musca F. Violi C. Alessandri E. Vezza 《European journal of haematology》1982,29(3):235-240
Effects of subcutaneous calcium-heparin and vitamin K administration were studied in 30 cirrhotic patients showing low values of prothrombin time, antithrombin III, fibrinogen, platelet count, plasminogen, a2-antiplasmin, raised levels of fibrin(ogen) degradation products and prolonged activated partial thromboplastin time. A group of 10 patients was first treated with K vitamin for 15 d; after vitamin K therapy interruption, a treatment with 5000 IU (8000 IU in 1 patient) every 12 h of subcutaneous calcium-heparin was started. In another group of 20 patients a treatment with 5000 IU (8000 IU in 2 patients) every 12 h of subcutaneous calcium-heparin was started immediately. The heparin administration in both groups had been performed for at least 2 weeks. No significant changes of blood coagulation picture were observed after vitamin K administration, while calcium-heparin treatment showed an increase in prothrombin time, fibrinogen, platelet count, plasminogen, a2-antiplasmin, a decrease in fibrin(ogen) degradation products and a shortened activated partial thromboplastin time. There was no significant change in antithrombin III values. 相似文献
8.
Teresa Vezza Jos Garrido-Mesa Patricia Diez-Echave Laura Hidalgo-García Antonio J. Ruiz-Malagn Federico García Manuel Snchez Marta Toral Miguel Romero Juan Duarte Enrique Guillamn Alberto Baos Rocío Morn Julio Glvez Alba Rodríguez-Nogales María Elena Rodríguez-Cabezas 《Nutrients》2021,13(8)
Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome. 相似文献
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10.
Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to susceptibility to oral lichen planus 总被引:6,自引:0,他引:6
Carrozzo M Uboldi de Capei M Dametto E Fasano ME Arduino P Broccoletti R Vezza D Rendine S Curtoni ES Gandolfo S 《The Journal of investigative dermatology》2004,122(1):87-94
Most lymphocytes in the lamina propria of oral lichen planus (OLP) lesions express and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), whereas they do not secret interleukin-4 and -10 or transforming growth factor-beta. We analyzed whether the polymorphisms of several cytokines may influence the susceptibility to OLP. Cytokine typing was performed by a sequence-specific PCR assay. Thirteen cytokine genes with 22 single-nucleotide polymorphisms were studied. IFN-gamma UTR 5644 genotype frequencies showed a significant increase in number of T/T homozygotes in OLP patients compared with controls (40.9 vs. 22.9%; p=0.0022). Moreover, in OLP patients, the frequency of the -308A TNF-alpha allele was higher than in the controls (21.6 vs. 9.3%; p < 0.05) causing a significantly increased frequency of the genotype G/A in OLP (43.2 vs. 14.3%; p=0.0002). Because in patients with mucocutaneous lichen planus (LP), the frequency of the -308A TNF-alpha allele was more than double the values in the pure OLP patients (40.9 vs. 15.1%; p=0.003), the -308G/A TNF-alpha genotype showed a significantly higher frequency in patients with mucocutaneous LP than in patients with pure OLP (81.8 vs. 30.3%, p=0.003). In conclusion, we suggest that genetic polymorphism of the first intron of the promoter gene of IFN-gamma may be an important risk factor to develop oral lesions of LP, whereas an increase in the frequency of -308A TNF-alpha allele may best contribute to the development of additional skin involvement. 相似文献