白介素27

白介素27(IL-27)是一种由p28和Ebi3组成异源二聚体的新型白介素,它能作用于活化的T细胞和NK细胞并增强IL-l2介导IFN-γ的产生,已鉴定WSX-1／TCCR为其受体的一个亚基。     

Characterization of brevicin 27, a bacteriocin synthetized byLactobacillus brevis SB27

Lactobacillus brevis SB27, isolated from sausages, produced an antimicrobial substance active against numerous strains of heterofermentative lactobacilli and against some strains of pediococci andBacillus. The antibacterial agent was shown to be heat stable, resistant over a wide pH range, and sensitive to proteolytic enzymes. It was identified as a bacteriocin and termed brevicin 27. Dialysis and ultrafiltration suggested an apparent molecular weight between 10 and 30 kDa for the crude inhibitory molecule. Brevicin 27 exhibited a hydrophobic character. A partially purified preparation, resulting from ammonium sulfate precipitation and cation exchange chromatography, permitted confirmation of some characteristics of the bacteriocin, previously established with the crude extract. After treatment of the original brevicin 27-producing strain with novobiocin, a nonproducing mutant was obtained. This mutant was sensitive to brevicin 27, and its plasmid profile revealed the loss of a plasmid of about 3 MDa.     

Hepatic microsomal enzyme induction by 2, 2', 3, 3', 4, 4'- and 2, 2', 3', 4, 4', 5-hexachlorobiphenyl

In an attempt to resolve conflicting reports in the literature, the effects of 2, 2', 3, 3', 4, 4'-hexa- and 2, 2', 3', 4, 4', 5-hexachlorobiphenyl on the hepatic microsomal drug-metabolizing enzymes were evaluated in the immature male rat. By comparison with the effects of the classical enzyme inducers, phenobarbitone (PB) and 3-methylcholanthrene (MC), 2, 2', 3, 3', 4, 4'-hexachlorobiphenyl, irrespective of its synthetic route, exhibited PB- and MC-type characteristics; the most prominent feature of the latter being a seven-fold increase in 4-chlorobiphenyl hydroxylase activity. 2, 2', 3', 4, 4', 5-Hexachlorobiphenyl also resembled a mixed (PB + MC)-type inducer although its MC-type characteristics were more pronounced than those of 2, 2', 3, 3', 4, 4'-hexachlorobiphenyl.     

PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest

Mechanisms linking mitogenic and growth inhibitory cytokine signaling and the cell cycle have not been fully elucidated in either cancer or in normal cells. Here we show that activation of protein kinase B (PKB)/Akt, contributes to resistance to antiproliferative signals and breast cancer progression in part by impairing the nuclear import and action of p27. Akt transfection caused cytoplasmic p27 accumulation and resistance to cytokine-mediated G1 arrest. The nuclear localization signal of p27 contains an Akt consensus site at threonine 157, and p27 phosphorylation by Akt impaired its nuclear import in vitro. Akt phosphorylated wild-type p27 but not p27T157A. In cells transfected with constitutively active Akt(T308DS473D)(PKB(DD)), p27WT mislocalized to the cytoplasm, but p27T157A was nuclear. In cells with activated Akt, p27WT failed to cause G1 arrest, while the antiproliferative effect of p27T157A was not impaired. Cytoplasmic p27 was seen in 41% (52 of 128) of primary human breast cancers in conjunction with Akt activation and was correlated with a poor patient prognosis. Thus, we show a novel mechanism whereby Akt impairs p27 function that is associated with an aggressive phenotype in human breast cancer.     

Biogenesis of mitochondria 27

Summary The isolation and characterization of five new mutants affecting mitochondrial protein synthesis in S. cerevisiae is reported. Each mutation confers in vivo resistance to the macrolide antibiotic spiramycin which acts by inhibiting mitochondrial protein synthesis in sensitive yeast. The mutants are distinguishable on the basis of their in vivo cross resistance to other antibiotics, their biochemical properties and genetic behaviour. Genetic analysis indicates the mode of inheritance to be nuclear for one mutation and cytoplasmic for the other four. Recombination analysis performed on crosses between different cytoplasmic determinants, together with data from monofactorial crosses of each determinant with sensitive strains, demonstrates at least two and possibly three cytoplasmic genetic loci conferring spiramycin resistance.The protein synthesizing activities of mitochondria isolated from the mutant strains range in response to spiramycin and other antibiotics from strong resistance through partial resistance to complete sensitivity. Based on this data the mutants showing strong antibiotic resistance in vitro might be simply classified as mitochondrial ribosome mutants and mutants sensitive in vitro as mitochondrial membrane mutants; however mutants showing partial resistances are not so readily accommodated in either class. The diverse biochemical properties cannot be correlated with the different genetic loci described; indeed three mutations, each resulting in different biochemical behaviour appear to occur at the same locus. The results are interpreted as providing further evidence for an earlier proposal of mitochondrial membrane-ribosome interactions.     

Alcaloides d'Araliopsis soyauxii. Isolement d'un nouvel alcaloide,l'Araliopsine

Six alkaloids have been isolated from root bark of Araliopsis soyauxii. Five are known, maculine, flindersiamine, skimmianine, (?) ribalinine, (+) isoplatydesmine and the sixth, araliopsine is new; its structure has been established as hydroxyisopropyldihydrofuro-2-quinolone. From the trunk bark four alkaloids have been isolated: flindersiamine, kokusaginine (?) ribalinine, (+) isoplatydesmine.     

L'ancistrocladonine et L'ancistroealaensine deux alcaloides nouveaux isoles de L'Ancistrocladus ealaensis

Ancistrocladonine and Ancistroealaensine are two new alcaloids isolated from the roots of Ancistrociadus ealaensis. In their UV spectrum they show strong resemblance to 1,8-dimethoxy naphthalene. Their structures were determined on the basis of spectral data of the bases and their Hofmann degradation products.     

Expression of sterol 27-hydroxylase (CYP27A1) enhances cholesterol efflux

Cholesterol efflux from CHOP cells transfected with sterol 27-hydroxylase (CYP27A1) was compared with non-transfected and mock-transfected cells. Transfection caused expression of CYP27A1, formation of 27-hydroxycholesterol, and inhibition of cholesterol biosynthesis. Transfection enhanced cholesterol efflux to apolipoprotein A-I or human plasma by 2-3-fold but did not affect the efflux in the absence of acceptor. The analysis of released sterols revealed that 27-hydroxycholesterol represented only a small proportion of sterols, most of which was non-oxidized cholesterol. Time course and dose dependence studies showed that expression of CYP27A1 in CHOP cells mostly affected the efflux of the "fast" cholesterol pool, and relatively more cholesterol was released with low concentrations of an acceptor. Preincubation of non-transfected cells with exogenous 27-hydroxycholesterol (10(-9) and 10(-7) m) led to the stimulation of cholesterol efflux by 24-60%. Expression of CYP27A1 in CHOP cells did not affect ABCA1 expression and abundance of ABCA1 protein. Thus, introduction of CYP27A1 into cells stimulates cholesterol efflux and therefore may increase protection against atherosclerosis.     

Modulation of heat-shock protein 27 (Hsp27) anti-apoptotic activity by methylglyoxal modification

Methylglyoxal (MG) is one of the side-products in glycolysis, and it reacts with proteins under physiological conditions. Here, we identified heat-shock protein 27 (Hsp27) as a major MG-modified protein in cells. MG modification of Hsp27 selectively occurs at Arg-188 to form argpyrimidine, and mutation in the residue represses the formation of a large oligomer. This modification process is essential to its repressing activity for cytochrome c-mediated caspase activation. Inhibition of MG modification of Hsp27 causes sensitization of the cells to anti-tumor drug-induced apoptosis. Thus, MG is a novel modulator of cell survival by directly incorporating with the specific protein residue.