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51.
The activity of rRNA methylases was stimulated by high-energy precursors of RNA (ribonucleoside triphosphates) and inhibited by degradation products of RNA (ribonucleotides and oligoribonucleotides). The response of methylases from rat Novikoff ascites tumor and liver to these metabolites was strikingly different. The highly active tumor enzymes responded preferentially to inhibition by catabolic metabolites, whereas the less active liver enzymes responded exclusively to stimulation by anabolic metabolites. When the activity of rRNA methylases was assayed in response to increasing concentration of S-adenosylmethionine, the tumor enzymes responded with a hyperbolic substrate dependence curve and the liver enzymes with a sigmoidal curve. In the presence of an inhibitory dinucleotide, ApA, the tumor enzymes responded with a sigmoidal curve; in the presence of a stimulator, adenosine 5'-triphosphate, the liver enzymes responded with a hyperbolic substrate concentration curve. When normal rats were subject to a series of treatments by thioacetamide, a hepatocarcinogen, the liver nucleolar rRNA methylases became responsive to inhibition by ApA and relatively unresponsive to stimulation by adenosine 5'-triphosphate. When tumor-bearing rats were treated with polyinosinate:polycytidylate, an antitumor agent, the tumor nucleolar rRNA methylases became unresponsive to inhibition by ApA and more responsive to stimulation by adenosine 5'-triphosphate. A correlation was noted between increased methylation efficiency in vivo and increased stability of nucleolar RNA during incubation in vitro, or vice versa. These results are interpreted to indicate that rRNAmethylases are regulated by cellular metabolites during the nucleolar biosynthesis of ribosomes and that rRNA methylases may provide a favorable site for selective action by cancer chemotherapeutic agents. 相似文献
52.
NK and CD4 cells collaborate to protect against melanoma tumor formation in the brain 总被引:2,自引:0,他引:2
Prins RM Vo DD Khan-Farooqi H Yang MY Soto H Economou JS Liau LM Ribas A 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(12):8448-8455
NK cells represent a potent immune effector cell type that have the ability to recognize and lyse tumors. However, the existence and function of NK cells in the traditionally "immune-privileged" CNS is controversial. Furthermore, the cellular interactions involved in NK cell anti-CNS tumor immunity are even less well understood. We administered non-Ag-loaded, immature dendritic cells (DC) to CD8alpha knockout (KO) mice and studied their anti-CNS tumor immune responses. DC administration induced dramatic antitumor immune protection in CD8alpha KO mice that were challenged with B16 melanoma both s.c. and in the brain. The CNS antitumor immunity was dependent on both CD4+ T cells and NK cells. Administration of non-Ag-loaded, immature DC resulted in significant CD4+ T cell and NK cell expansion in the draining lymph nodes at 6 days postvaccination, which persisted for 2 wk. Finally, DC administration in CD8alpha KO mice was associated with robust infiltration of CD4+ T cells and NK cells into the brain tumor parenchyma. These results represent the first demonstration of a potent innate antitumor immune response against CNS tumors in the absence of toxicity. Thus, non-Ag-loaded, immature DC administration, in the setting of CD8 genetically deficient mice, can induce dramatic antitumor immune responses within the CNS that surpass the effects observed in wild-type mice. Our results suggest that a better understanding of the cross-talk between DC and innate immune cells may provide improved methods to vaccinate patients with tumors located both systemically and within the CNS. 相似文献
53.
In the present study, the roles of telomerase and prostaglandin E(2) (PGE(2)) in platelet-derived growth factor (PDGF's) and fibroblast growth factor-2 (FGF-2's) effects against C(2)-ceramide-induced cell death were investigated. C(2)-ceramide reduced the viability of NIH3T3 cells in a condition without calf serum (CS) in accordance with decreasing telomerase activity according to the TRAP assay. The addition of CS significantly protected cells from C(2)-ceramide-induced apoptosis through increased telomerase activity, and the phosphorylations of PDGF and the FGF-2-like receptor in NIH3T3 cells were detected. Adding PDGF and FGF-2 decreased the cytotoxic effect elicited by C(2)-ceramide through stimulating telomerase activity, which was blocked by adding a telomerase inhibitor (TI). Activations of ERKs and JNKs were detected in PDGF- and FGF-2-treated NIH3T3 cells, and the telomerase activities induced by PDGF and FGF were respectively inhibited by the addition of the ERK inhibitor, PD98059, and the JNK inhibitor, SP600125. Accordingly, induction of cyclooxygenase-2 (COX-2) protein expression and PGE(2) production was detected in PDGF- and FGF-2-treated NIH3T3 cells, and the telomerase activities stimulated by PDGF and FGF were reduced by adding a specific COX-2 inhibitor, NS398, through a decrease in PGE(2) production. Incubation of cells with PGE(2) or the EP1 agonist, 17-PT, but not the EP2 agonist, sulprostone, the EP3 agonist, butaprost, or the EP4 agonist, PGE(1) alcohol, significantly enhanced the telomerase activity of NIH3T3 cells. PGE(2) protection of NIH3T3 cells against C(2)-ceramide-induced cell death was identified by the MTT and LDH-release assays, and it was inhibited by adding the EP1 antagonist, SC-19220. Ceramide metabolites including ceramide-1-phosphate (C1P) and sphingosine-1-phosphate (S1P), and a standard control of exogenous ceramide C(2)-dihydroceramide show no effect on the telomerase activity and viability of NIH3T3 cells. The involvement of COX-2/PGE(2)-mediated telomerase activation by PDGF and FGF-2 against C(2)-ceramide-induced cell death is first demonstrated herein. 相似文献
54.
We studied the biochemical degradation of organic matter comprising marine diatom, land grass, and salt marsh plant in estuarine
ecosystems in two laboratory microcosms consisting of estuarine sediments and coastal seawater. The materials were incubated
separately and together under controlled oxic and anoxic conditions to test effects of co-metabolism and redox on overall
degradation of organic matter. We followed variations of bulk parameters [total organic carbon (TOC), total nitrogen (TN),
C/N ratio, δ13CTOC, and δ15NTN], fatty acid concentrations, and compound-specific δ13C values over 3 months. Coexistence of marine diatom (relatively labile) with land grass/salt marsh plant (relatively refractory)
in the microcosms yielded a negative co-metabolism effect (retardation rather than acceleration) on the overall degradation
of organic matter. The ratios of oxic to anoxic degradation rate constants (k
ox/k
an) of TOC and most fatty acids were in a range of 1.1–1.7, implying that redox conditions per se had a limited influence on
degradation of fresh organic materials in estuarine ecosystems. Variations of two bacteria-specific fatty acids (iso- and
anteiso-15:0) and their δ13C values indicated that bacterial metabolism could use organic carbon (OC) from any available material when only one single-source
material was dominant in the ecosystems. However, bacteria probably utilized OC preferentially from labile marine diatom when
multiple-source materials were almost equally present in the ecosystems. 相似文献
55.
The discovery that OmpF was related to the transportation of ruthenium complexes through cell membrane was achieved with proteomics technologies. An integral ruthenium complex exists inside the cell as identified by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. An inhibition assay with Escherichia coli was used to demonstrate the relationship between the transportation of the polypyridyl ruthenium complexes and the presence of OmpF (outer membrane protein F). For instance, the amount of [Ru(tpy)(bpy)Cl]+ (tpy: teripyridine; bpy: bipyridine) that entered the cells was determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) of cell extracts and was measured to be approximately 0.55 μM. In the presence of 10% sucrose solution which is known to reduce the OmpF concentration, the ruthenium complex concentration was reduced to approximately 0.28 μM, which is a 50% reduction. These data suggest that OmpF plays a key role in the transportation of positively charged polypyridyl chlororuthenium complexes into E. coli. 相似文献
56.
Chicken embryo fibroblasts(CEFs)are among the most commonly used cells for the study of interactions between chicken hosts and H5N1 avian influenza virus(AIV).In this study,the expression of eleven housekeeping genes typically used for the normalization of quantitative real-time PCR(QPCR)analysis in mammals were compared in CEFs infected with H5N1 AIV to determine the most reliable reference genes in this system.CEFs cultured from 10-day-old SPF chicken embryos were infected with 100 TCID50 of H5N1 AIV and harvested at 3,12,24 and 30 hours post-infection.The expression levels of the eleven reference genes in infected and uninfected CEFs were determined by real-time PCR.Based on expression stability and expression levels,our data suggest that the ribosomal protein L4(RPL4)and tyrosine 3-monooxygenase tryptophan 5-monooxygenase activation protein zeta polypeptide(YWHAZ)are the best reference genes to use in the study of host cell response to H5N1 AIV infection.However,for the study of replication levels of H5N1 AIV in CEFs,the β-actin gene(ACTB)and the ribosomal protein L4(RPL4)gene are the best references. 相似文献
57.
ABA诱导玉米叶质外体H2O2积累的机制 总被引:6,自引:0,他引:6
通过组织化学染色和电镜观察并结合酶活性分析表明,ABA可通过诱导玉米(Zea mays L、)叶片质膜NADPH氧化酶、细胞壁POD及质外体PAO活性的升高,使其质外体产生H2O2;其中质膜NADPH氧化酶起主要作用。 相似文献
58.
59.
Chou DS Chan CH Hsiao G Shen MY Tsai YJ Chen TF Sheu JR 《Journal of biomedical science》2006,13(3):333-343
Summary The intracellular mechanisms underlying oxidized low-density lipoprotein (oxLDL)-signaling pathways in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of oxLDL in prevention of platelet aggregation. In this study, oxLDL concentration-dependently (40–120 g/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 g/ml) markedly decreased the fluorescence intensity of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (150 nM). This phosphorylation was markedly inhibited by oxLDL (40 and 80 g/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 g/ml) markedly increased levels of cyclic AMP and cyclic AMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. The thrombin-evoked increase in pHi was inhibited in the presence of oxLDL (40 and 80 g/ml). These results indicate that the antiplatelet activity of oxLDL may involve the following pathways. (1) oxLDL may initially induce conformational changes in platelet membranes, leading to inhibition of the activation of protein kinase C, followed by inhibition of P47 protein phosphorylation, and intracellular Ca2+ mobilization. (2) oxLDL also activated formation of cyclic AMP and cyclic AMP-induced VASP Ser157 phosphorylation, resulting in inhibition of the Na+/H+exchanger; this leads to reduced intracellular Ca2+ mobilization, and ultimately to inhibition of platelet aggregation. This study further provides new insights concerning the effects of low concentrations of oxLDL on platelet aggregation. 相似文献
60.