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101.
102.
Millie Hughes-Fulford 《Journal of cellular biochemistry》1994,54(3):265-272
Our previous studies have implied that prostaglandins inhibit cell growth independent of cAMP. Recent reports, however, have suggested that prostaglandin arrest of the cell cycle may be mediated through protein kinase A. In this report, in order to eliminate the role of c-AMP in prostaglandin mediated cell cycle arrest, we use the-49 lymphoma variant (cyc?) cells that lack adenylate cyclase activity. We demonstrate that dimethyl prostaglandin A1 (dmPGA1) inhibits DNA synthesis and cell growth in cyc? cells. DNA synthesis is inhibited 42% by dmPGA1 (50 μM) despite the fact that this cell line lacks cellular components needed for cAMP generation. The ability to decrease DNA synthesis depends upon the specific prostaglandin structure with the most effective form possessing the α,β unsaturated ketone ring. Dimethyl PGA1 is most effective in inhibiting DNA synthesis in cyc? cells, with prostaglandins PGE1 and PGB1 being less potent inhibitors of DNA synthesis. DmPGE2 caused a significant stimulation of DNA synthesis. S-49 cyc- variant cells exposed to (30–50 μm) dmPGA1, arrested in the G1 phase of the cell cycle within 24 h. This growth arrest was reversed when the prostaglandin was removed from the cultured cells; growth resumed within hours showing that this treatment is not toxic. The S-49 cyc? cells were chosen not only for their lack of adenylate cyclase activity, but also because their cell cycle has been extensively studied and time requirements for G1, S, G2, and M phases are known. Within hours after prostaglandin removal the cells resume active DNA synthesis, and cell number doubles within 15 h suggesting rapid entry into S-phase DNA synthesis from the G1 cell cycle block. The S-49 cyc? cells are known to have a G1/S boundary through M phase transition time of 14.8 h, making the location of the prostaglandin cell cycle arrest at or very near the G1/S interface. The oncogenes, c-fos and c-myc which are normally expressed during G1 in proliferating cells have a 2–3 fold enhanced expression in prostaglandin G1 arrested cells. These data using the S-49 variants demonstrate that dmPGA1 inhibits DNA synthesis and arrests the cell cycle independent of cAMP-mediated effects. The prostaglandin arrested cells maintain the gene expression of a G1 synchronous cell which suggests a unique molecular mechanism for prostaglandin action in arresting cell growth. These properties indicate that this compound may be an effective tool to study molecular mechanisms of regulation of the cell cycle. 相似文献
103.
The relationship between synthesis and N-liked glycosylation site occupancy of recombinant human prolactin produced from C127 cells was studied with the aid of a battery of protein synthesis inhibitors. Non-lethal concentrations of sodium fluoride, gougerotin, puromycin, anisomycin, and emetine did not alter site occupancy, but low concentrations (<10g ml–1) of cycloheximide increased the fraction of secreted prolactin bearing oligosaccharide from 20% to 80% of the total. Cycloheximide is an inhibitor of the elongation step of protein synthesis. The observed increase in glycosylation site occupancy upon addition of cycloheximide is consistent with the current opinion that the initial glycosylation event occurs cotranslationally during a limited time period. Cycloheximide may extend this time period by reducing elongation rate. However, the absence of any effect from treatment with other inhibitors of elongation suggests that cycloheximide is unique in its behavior on this system.Abbreviations clp-PRL
clipped form of prolactin
- DMEM/F12
11 Dulbecco's Modified Eagle's Medium/Ham's nutrient mixture F12
- G-PRL
glycosylated (N-linked) fraction of prolaction
- NG-PRL
prolactin fraction without N-linked glycosylation
- PMSF
phenylmethylsulfonylfluoride 相似文献
104.
The degradation of dichloromethane by the pure strainHyphomicrobium GJ21 and by an enrichment culture, isolated from a continuously operating biological trickling filter system, as well as the corresponding growth rates of these organisms were investigated in several batch experiments. By fitting the experimental data to generally accepted theoretical expressions for microbial growth, the maximum growth rates were determined. The effect of NaCl was investigated at salt concentrations varying from 0 to 1000 mM. Furthermore the dichloromethane degradation was investigated separately in experiments in which a high initial biomass concentration was applied. The results show that microbial growth is strongly inhibited by increased NaCl concentrations (50% reduction of max at 200–250 mM NaCl), while a certain degree of adaptation has taken place within an operational system eliminating dichloromethane. A critical NaCl concentration for growth of 600 mM was found for the microbial culture isolated from an operational trickling filter, while a value of 375 mM was found for the pure cultureHyphomicrobium GJ21. The substrate degradation appears to be much less susceptible to inhibition by NaCl. Even at 800 mM NaCl relatively high substrate degradation rates are still observed, although this process is again dependent on the NaCl concentration. Here the substrate elimination is due to the maintenance requirements of the microorganisms. The inhibition of the dichloromethane elimination was also investigated in a laboratory scale trickling filter. The results of these experiments confirmed those obtained in the batch experiments. At NaCl concentrations exceeding 600 mM a considerable elimination of dichloromethane was still observed for during several months of operation. These observations indicate that the inhibition of microbial growth offers a significant control parameter against excessive biomass growth in biological trickling filters for waste gas treatment. 相似文献
105.
用浅麻醉的Wistar大鼠40只,以辐射热照尾作为伤害性刺激,经玻璃微电极引导尾核痛兴奋神经元(PEN)和痛抑制神经元(PIN)的放电,同时测量甩尾反射潜伏期(TFL)作为甩尾痛阈的指标。结果表明:(1)自然状态下辐射热照尾引起尾核中PEN放电频率增加和PIN放电频率减少与甩尾反射(TF)相伴行。放电变化发生在TF之前,结束在TF之后,PEN和PIN放电变化与TFL呈高度正相关。(2)辐射热照尾同时引起一侧尾核PEN放电频率增加和另一侧PIN放电频率减少,二者协同活动,并发生在TF之前,结束在TF之后。(3)侧脑室注射55μg/10μl吗啡呈镇痛作用时,尾核PEN放电频率减少和PIN放电频率增加,放电变化仍发生在TF之前,结束在TF之后。结果提示,尾核中PEN、PIN放电和TF是中枢不同水平同时对痛觉调制所产生的结果。 相似文献
106.
苏文金 《中国微生态学杂志》1994,(4)
本工作测试了7种吩噻嗪衍生物在体外对5株好氧或兼性厌氧菌和89株厌氧菌的最小抑菌浓度,结果表明,吩噻嗪衍生物对细菌(尤其是球菌和厌氧菌)具有一定的抑制作用,但携带可拮抗艰难梭菌肠道定植屏障菌群的悉生小鼠接受2周或4周的Chlorpromazine(0.2mg/小鼠/天)并不会使菌群屏障遭破坏。 相似文献
107.
鸭肝脂肪酸合成酶的NADPH底物抑制及作用动力学 总被引:7,自引:0,他引:7
己知动物脂肪酸合成酶的底物乙酰辅酶A和丙二酰辅酶A具有竞争性双底物抑制的乒乓机制。实验发现鸭肝脂肪酸合成酶的第三个底物NADPH也具有底物抑制,并研究了它的规律及与NADPH有关的稳态动力学。发现对于该酶的全反应,增加丙二酰辅酶A浓度,降低环境盐浓度,均使NADPH底物抑制减少。但以NADPH作底物的酮酰还原和烯酰还原二步单独反应以及包含四步单独反应的乙酰乙酰辅酶A还原反应都无NADPH底物抑制现象。NADPH底物抑制对丙二酰辅酶A为竞争性,丙二酰辅酶A底物抑制对NADPH为非竞争性。在全反应中NADPH和丙二酰辅酶A之间发现为乒乓机制,在乙酰乙酰辅酶A还原反应中,两个底物NADPH和乙酰乙酰辅酶A之间则表现为序列反应机制。降低环境盐浓度使NADPH和丙二酰辅酶A之间的乒乓机制向序列机制转化。在全反应中,NADP产物抑制相对NADP为竞争性,对丙二酰辅酶A为非竞争性。 相似文献
108.
ANTONIO OSUNA NIEVES RODRIGUEZ-CABEZAS FRANCISCO GAMARRO CARMEN MASCARO 《The Journal of eukaryotic microbiology》1994,41(3):231-236
ABSTRACT. We have studied the action of diphtheria toxin, modeccin and ricin on HeLa cells infected by Trypanosoma cruzi . Parasitized HeLa cells were resistant to diphtheria toxin and modeccin, whereas non-parasitized cells from the same cultures and control cultures showed cytopathological alterations. Protein synthesis, assayed by the incorporation of labelled methionine, diminished in toxin-treated control cultures but remained unaltered in the infected ones, compared to synthesis by untreated infected cells. Ricin, on the other hand, is a toxin that enters the cytoplasm by endocytosis. It has greater cytopathological effects in parasitized cells than in non-parasitized ones from the same cultures or uninfected control cells. Protein synthesis was inhibited in infected cultures treated with ricin. 相似文献
109.
Richard D. Griner Rick G. Schnellmann 《In vitro cellular & developmental biology. Animal》1994,30(1):30-34
Summary We have previously shown that shaking the culture plates (SHAKE) of rabbit renal proximal tubule cells (RPTC) to maintain
adequate aeration increased aerobic metabolism and decreased the induction of glycolysis compared to RPTC cultured under standard
conditions (STILL). However, glycolysis in SHAKE RPTC remained elevated compared to glycolysis in proximal tubules in vivo.
In the present study the contribution of culture medium sugar composition and concentration to glycolytic metabolism was assessed
in RPTC. SHAKE and STILL RPTC cultured in 5 mM glucose contained lactate levels equivalent to the respective SHAKE and STILL RPTC cultured in standard culture medium which
contains 17.5 mM glucose. Similarly, the activity of lactate dehydrogenase was unchanged by lowering the medium glucose concentration. Substituting
5 mM galactose for 5 mM glucose in the culture medium significantly reduced the lactate content of both SHAKE and STILL RPTC but had no effect on
lactate dehydrogenase activity. Cell growth was equivalent under all culture conditions. Sensitivity to mitochondrial inhibition
was determined for each culture condition by measuring cell death after exposure to the respiratory inhibitor antimycin A.
The results showed a hierarchy of sensitivity to antimycin A (5 mM galactose SHAKE >5 mM glucose SHAKE >17.5 mM glucose SHAKE = 17.5 mM glucose STILL), which was generally inversely correlated with the level of glycolysis as measured by lactate content (17.5
mM glucose STILL >17.5 mM glucose SHAKE = 5 mM glucose SHAKE >5 mM galactose SHAKE). 相似文献
110.
William R. Gower Jr. Robert M. Risch Constantine V. Godellas Peter J. Fabri 《In vitro cellular & developmental biology. Animal》1994,30(3):151-161
Summary A new human pancreatic cancer (HPAC) cell line was established from a nude mouse xenograft (CAP) of a primary human pancreatic
ductal adenocarcinoma. In culture, HPAC cells form monolayers of morphologically heterogenous, polar epithelial cells, which
synthesize carcinoembryonic antigen, CA 19-9, CA-125, cytokeratins, antigens for DU-PAN-2, HMFG1, and AUA1, but do not express
chromogranin A or vimentin indicative of their pancreatic ductal epithelial cell character. In the presence of serum, HPAC
cell DNA synthesis was stimulated by insulin, insulin growth factor-I, epidermal growth factor, and TGF-α but inhibited
by physiologic concentrations of hydrocortisone and dexamethasone. Dose-dependent inhibition of DNA synthesis was limited
to steroids with glucocorticoid activity. The inhibitory effect of dexamethasone was abolished by the glucocorticoid antagonist
RU 38486. Binding of [3H]dexamethasone to cytosolic proteins was specific and saturable at 4° C. Scatchard analysis of binding data demonstrated
a single class of high-affinity binding sites (Kd=3.8±0.9 nM; Bmax=523±128 fmol/mg protein). Western blot analysis revealed a major protein band that migrated at a Mr of 96 kDa. Northern blot analysis identified an mRNA of approximately 7 kilobases which hybridized with a specific glucocorticoid
receptor complementary DNA probe (OB7). These findings support a role for glucocorticoids in the regulation of human malignant
pancreatic cell function. 相似文献