蓖麻毒蛋白的改性与抗癌活性

蓖麻毒蛋白对细胞杀伤是非特异性的，因此有严重的毒副作用．文章对蓖麻毒蛋白的改性及改性后的抗肿瘤活性进行了综述，并对由蓖麻毒蛋白构建的免疫毒素在肿瘤的治疗中显示出的良好应用前景进行了讨论．     

Participation of c-myc protein in DNA synthesis of human cells

The protein product of oncogene c-myc is believed to be important in regulation of the cell cycle. However, its direct role in DNA synthesis has not been explored. Experiments presented here show that the addition of affinity-purified antibodies against the human c-myc protein to nuclei isolated from several types of human cells reversibly inhibited DNA synthesis and DNA polymerase activity of these nuclei. This suggests that c-myc encodes a protein that is functionally involved in DNA synthesis.     

Pertussis toxin-sensitive pathway in the stimulation of c-myc expression and DNA synthesis by bombesin

The bombesin-like peptides are potent mitogens for Swiss 3T3 fibroblasts, human bronchial epithelial cells, and cells isolated from small cell carcinoma of the lung. The mechanism of signal transduction in the proliferative response to bombesin was investigated by studying the effect of Bordetella pertussis toxin on bombesin-stimulated mitogenesis. At nanomolar concentrations, bombesin increased levels of c-myc messenger RNA and stimulated DNA synthesis in Swiss 3T3 cells. Treatment of the cells with pertussis toxin (5 nanograms per milliliter) completely blocked bombesin-enhanced c-myc expression and eliminated bombesin-stimulated DNA synthesis. This treatment had essentially no effect on the mitogenic responses to either platelet-derived growth factor or phorbol 12,13-dibutyrate. These results suggest that the mitogenic actions of bombesin-like growth factors are mediated through a pertussis toxin-sensitive guanine nucleotide-binding protein. Furthermore they indicate that bombesin-like growth factors act through pathways that are different from those activated by platelet-derived growth factor.     

Biologically active chorionic gonadotropin: synthesis by the human fetus

The kidney, and to a slight extent the liver, of human fetuses were found to synthesize and secrete the alpha subunit common to glycoprotein hormones. Fetal lung and muscle did not synthesize this protein. Since fetal kidney and liver were previously found to synthesize beta chorionic gonadotropin, their ability to synthesize bioactive chorionic gonadotropin was also determined. The newly synthesized hormone bound to mouse Leydig cells and elicited a biological response: namely, the synthesis of testosterone. These results suggest that the human fetus may participate in metabolic homeostasis during its development.     

Reversal of catecholamine refractoriness by inhibitors of RNA and protein synthesis

The generation of adenosine 3',5'-monophosphate (cyclic AMP) in response to catecholamines in the 2B subclone of RGC6 rat glioma cells previously exposed to norepinephrine and refractory to further norepinephrine addition is substantially increased by addition of inhibitors of RNA and protein synthesis. The time course of the effect of these inhibitors on cyclic AMP concentration suggests that rapid protein synthesis and turnover are involved in catecholamine refractoriness. Norepinephrine induction of cyclic nucleotide phosphodiesterase is demonstrable in RGC6 cells but not in the 2B subclone. Thus, catecholamine refractoriness cannot be attributed to induction of phosphodiesterase. This implies that induction of a protein or proteins, important in catecholamine refractoriness, affects the synthesis rather than the degradation of cyclic AMP.     

High-frequency C-type virus induction by inhibitors of protein synthesis

When inhibitors of protein synthesis are added to BALB/c mouse cells in culture, induction of naturally integrated C-type RNA virus occurs in a high percentage of cells. The action of protein synthesis inhibitors differs from that of halogenated pyrimidines, another class of virus inducers, in their effects on biologically distinguishable viruses. The use of such inhibitors to study integrated virus expression provides a means for studying gene regulation in mammalian cells.     

Heterogeneity of normal human diploid fibroblasts: isolation and characterization of one phenotype

Cultures of human diploid fibroblasts contain cells that respond to exposure to the first component of complement (C1) by initiating DNA synthesis and growth. The plasma membranes of these cells have specific binding sites for the C1q subcomponent of C1. A fluorescence-activated cell sorter was used to isolate a subset of cells with a high affinity for C1q, and the growth and synthesis activities of these high-affinity cells were studied after numerous replications in vitro. These cells synthesize DNA and grow faster than the parent cultures and low-affinity cells, and they produce two to three times as much protein. About 40 percent of their total protein synthesis activity is directed to collagen production, unusually high proportions of collagen types III and V being produced. These properties and the high affinity of the cells for C1q are retained for at least six cell transfers. This phenotype has the properties expected of fibroblasts in healing wounds and inflamed tissues.     

Collagen synthesis by cells synchronously replicating DNA

Replication and the performance of a differentiated function have been considered antagonistic processes. When cells in culture are partially tially synchronized with 5-fluoro-2'-deoxyuridine (FUdR), the synthesis of the specialized protein (collagen) is not reduced during chromosomal replication (S period). Collagen synthesis varies with general protein synthesis through the S period.     

Chondroitin sulfate: inhibition of synthesis by puromycin

Puromycin reversibly inhibits synthesis of chondroitin sulfate by vertebral chondrocytes from 10-day-old chick embryos. Treatment of these cells with puromycin for 5 hours does not affect viability or capacity to multiply on subsequent release from their matrix. It is suggested that synthesis of this polysaccharide is coupled with that of protein; there may be a feedback control in its synthesis.     

Actinomycin D: inhibition of respiration and glycolysis

Actinomycin D inhibited respiration and anaerobic glycolysis of human leukemic leukocytes and lowered the adenosine triphosphate content of the cells. Inhibitory effects on respiration and on RNA synthesis could not be dissociated from one another over a wide range of drug concentrations. Actinomycin D also impaired protein synthesis, probably by decreasing the availability of adenosine triphosphate and by inhibiting messenger RNA.     

Specific inhibition of viral ribonucleic acid replication by Gliotoxin

Gliotoxin inhibits intracellular replication of poliovirus in HeLa cells at a stage subsequent to adsorption and penetration of virus. The sensitive step is synthesis of viral RNA: synthesis of viral protein is unaffected except as a consequence of blockade of RNA synthesis. Concentrations of gliotoxin sufficient to block viral RNA synthesis completely do not affect cellular RNA synthesis.     

Stimulation of RNA and protein synthesis by intracellular insulin

Like insulin-sensitive somatic cells, stage IV oocytes from Xenopus laevis increase their synthesis of RNA, protein, and glycogen in response to extracellular insulin. Synthesis of RNA and protein are also increased when oocytes are maintained under paraffin oil and insulin is microinjected into the cytoplasm. The effects of external and intracellular insulin are additive, suggesting separate mechanisms of action. Experiments with nuclei isolated under oil show that RNA synthesis can be stimulated by applying insulin to the nucleus directly. Thus, the nucleus appears to be one intracellular site of hormone action.     

伏马菌素B1诱导Marc-145细胞caspase非依赖型程序性细胞死亡

[目的]以Marc-145细胞为模型,研究了伏马菌素B1能否导致细胞产生其他类型程序性细胞死亡。[方法]利用caspase抑制剂、蛋白合成抑制剂、非凋亡程序性细胞死亡necroptosis抑制剂及ROS抑制剂,分别抑制caspase活性、蛋白质合成、necroptosis和ROS,采用结晶紫染色和AnnexinV-FITC/PI双染分析这些抑制剂对伏马菌素B1诱导Marc-145细胞死亡的影响。[结果]caspase、necroptosis抑制剂和2种自由基抑制剂不能抑制伏马菌素B1诱导的Marc-145细胞死亡,但蛋白合成抑制剂则可以显著抑制伏马菌素B1诱导的Marc-145细胞死亡。[结论]伏马菌素B1所诱导的Marc-145细胞的死亡是一种受基因表达调控的程序性细胞死亡,但与caspase、ROS和nec-roptosis无关。     

Adult hemoglobin synthesis by reticulocytes from the human fetus at midtrimester

The synthesis of adult-type hemoglobin was measured in small samples of peripheral blood cells from 9- to 18-week human fetuses. Hemoglobin indistinguishable from hemoglobin A was identified by ion-exchange chromatography, electrophoresis at pH 8.6, tryptic peptide analysis, and the insensitivity of its synthesis to the action of O-methylthreonine. Synthesis of hemoglobin A accounted for 8 to 14 percent of total hemoglobin synthesis and was demonstrated in as little as 10 microliters of fetal blood. These studies provide sensitive methods for the detection of beta chain types in hemoglobin synthesized by the human fetus at midtrimester. If methods to obtain small quantities of fetal blood at midtrimester become available, these techniques should be applicable to the antenatal detection of sickle cell anemia and related hemoglobinopathies.     

Inhibition of serum- and ras-stimulated DNA synthesis by antibodies to phospholipase C

Several immunologically distinct isozymes of inositol phospholipid-specific phospholipase C (PLC) have been purified from bovine brain. Murine NIH 3T3 fibroblasts were found to express PLC-gamma, but the expression of PLC-beta was barely detectable by radioimmunoassay or protein immunoblot. A mixture of monoclonal antibodies was identified that neutralizes the biological activity of both endogenous and injected purified PLC-gamma. When co-injected with oncogenic Ras protein or PLC-gamma, this mixture of antibodies inhibited the induction of DNA synthesis that characteristically results from the injection of these proteins into quiescent 3T3 cells. However, when oncogenic Ras protein or PLC-gamma was co-injected with a neutralizing monoclonal antibody to Ras, only the DNA synthesis induced by the Ras protein was inhibited--that induced by PLC was unaffected. These results suggest that the Ras protein is an upstream effector of PLC activity in phosphoinositide-specific signal transduction and that PLC-gamma activity is necessary for Ras-mediated induction of DNA synthesis.     

Repression of ornithine transcarbamylase protein formation by arginine

Arginine-repressed cells of Escherichia coli W do not form a protein immunologically related to ornithine transcarbamylase. This was determined by lack of cross-reactivity of repressed cell extracts with rabbit antisera prepared against purified ornithine transcarbamylase. The results indicate that arginine acts by blocking the synthesis of the entire enzyme-protein.     

Transformation of human lymphocytes: inhibition by homologous alpha globulin

An alpha globulin fraction prepared from normal human plasma by column chromatography prevents homologous lymphocyte transformation and the stimulation of DNA, and also protein synthesis induced by phytohemagglutinin and specific antigens. These observations support the concept of a normal circulating immunosuppressant factor which prevents lymphoid cell proliferation.