In vivo effects of immunostimulating lipopeptides on mouse liver microsomal cytochromes P-450 and on paracetamol-induced toxicity

Summary Immunomodulating lipopeptides lauroyl-L-Ala--D-Glu-LL-A2pmNH2-Gly (RP 44.102) and lauroyl-L-Ala--D-Glu-LL-A2pmNH2 (RP 56.142) were found to protect mice against the hepatotoxicity of paracetamol, which is due to cytochrome P-450 dependent formation of toxic metabolites and radicals. In fact they decreased the amount of hepatic microsomal cytochrome P-450, and the level of CCl₄-induced lipid peroxidation. In contrast lauroyl-L-Ala--D-Glu-DD-A2pmNH2 (RP 53.204), which only differs by the configuration of the two chiral carbons of A2pm (diaminopimelic acid) and is not an immunomodulating agent, failed to protect against poisoning by paracetamol and had no effect on the level of hepatic cytochrome P-450 or the microsomal CCl₄-induced lipid peroxidation. This provides a clear connection between the immunostimulating properties of a compound and its effects on xenobiotic biotransformations.     

Cyclophosphamide-impaired regulation of hepatic heme metabolism

Summary Im male rats hepatic cytochromes b₅ and P-450 were reduced at different times after treatment with cyclophosphamide (CP) (200 mg/kg i.p. for 3 days). In contrast, microsomal heme did not change until 48 h after the last dose of CP, leading to accumulation of heme in a non-cytochromal form. Parallel to the above changes the heme metabolism showed derangement: -aminolaevulinate synthase, the rate-limiting enzyme in heme synthesis, was depressed and heme oxygenase, the enzyme which catalyzes the oxidative degradation of heme, was increased.     

细胞色素P450酶生物转化及新催化反应的最新进展

细胞色素P450酶(P450s或CYPs)是一类广泛存在于生命体中,依赖于亚铁血红素催化多种底物的单加氧酶。一方面,它涉及许多高活性天然产物生物合成的关键步骤,对其生物转化研究有助于提高活性分子的产率和活性;另一方面,其催化涉及金属元素以及辅助因子,其蛋白质改造和新催化反应的研发也不断取得新突破。本文就细胞色素P450酶这两方面的最近研究进展进行了总结与论述。     

Diversity and dispersal history of the talitrids (Crustacea: Amphipoda: Talitridae) of Bermuda

Five taxa of talitrid amphipods were found in the archipelago of Bermuda, of which three were recorded there for the first time. Four of these are supralittoral wrack generalists: Platorchestia monodi BOLD:AAB3402, (a unique Molecular Operational Taxonomic Unit according to the Barcode Index Number system), a related species recognized by molecular methods, Platorchestia platensis BOLD:AAA2949, Mexorchestia carpenteri carpenteri BOLD:AAC1491 and Tethorchestia antillensis; and one a terrestrial leaf-litter generalist: Talitroides alluaudi. A key is provided to discriminate between the formally described talitrids of Bermuda. Dispersal mechanisms from the American continent to Bermuda were considered for all taxa based on species distributions along the North American Atlantic coast and also investigated by molecular methods, using genetic population differentiation and haplotype network analysis based on the barcode region of cytochrome c oxidase subunit I gene. For P. monodi BOLD:AAB3402 the genetic results suggest that some dispersal events occurred before human colonization of Bermuda but are equivocal about the source population and therefore the direction of dispersal. Some very recent synanthropic dispersal is possible with this species. For the other two species studied genetically, P. platensis BOLD:AAA2949 and M. c. carpenteri BOLD:AAC1491, the small population samples analysed support dispersal to Bermuda from the American mainland, before human occupation of Bermuda, although the available sample size was limited for these species. The available limited direct, non-genetic evidence supports synanthropic transport for Talitroides alluaudi. Platorchestia monodi BOLD:AAB3402 is found in the same wrack habitat as P. platensis BOLD:AAA2949 on Bermuda, apparently without interbreeding. No evidence was found that driftwood specialist talitrids had become established in Bermuda.     

冬眠及外源维生素C对中华鳖(Pelodiscus sinensis)稚鳖能量代谢的影响

观测了冬眠前饲料中添加外源维生素C(Vc)对冬眠中华鳖稚鳖能量代谢的影响.结果发现外源Vc不能提高冬眠期间中华鳖的存活率(P=0.57).稚鳖个体在冬眠期间生长能的平均值为-0.15 kJ.d-1,该值与代谢耗能相当.鳖体蛋白、脂肪、水分和灰分质量分数w在冬眠前后无显著差异(P>0.05),外源Vc对鳖的体组成没有明显影响(P>0.05).冬眠8周后,肝脏线粒体细胞色素C氧化酶(COX)和肝脏乳酸锐氢酶(LDH)的活性显著下降(P<0.05).饲料外源Vc对肝脏线粒体蛋白含量、肝脏线粒体COX和LDH的活性均无影响(P>0.05).     

Protein kinases mediate nitric oxide-induced apoptosis in the insect cell line IPLB-LdFB

The involvement of protein kinases (PKA, PKC and PKB) in nitric oxide (NO)-induced apoptosis with sodium nitroprusside plus N-acetyl-L-cysteine in the IPLB-LdFB cell line from the insect Lymantria dispar was investigated. The presence of protein kinase-like molecules was demonstrated by western blot analysis. The role of the kinases in programmed cell death was analysed in cytofluorimetric experiments by incubating the insect cells with H-89 (a specific inhibitor of PKA), calphostin C (an inhibitor of PKC) or wortmannin (an inhibitor of phosphatidylinositol 3-kinase). The results show that PKA is correlated with the induction and PKC and PKB with the prevention of NO-induced insect cell death. Moreover, NO-induced apoptosis involves the release of cytochrome c. Received 15 March 2002; accepted 25 March 2002     

Effects of H_2O_2 on Oxygen Supply in the Process of DCA Fermentation

IntroductionLong chainα,ω- dicarboxylic acids (DCA ) areversatile chemical intermediates used as rawmaterials for the preparation of perfumes,polymers,and adhesives[1] .Various strains of C.tropicalis are known to produce DCA whencultured with alkanes or fatty acids as the carbonsource[2 ,3] .　During aerobic and viscous fermentation,theoxygen supply is of crucial importance becauseinsufficient oxygen can lead to suboptimalproductivities[4 ] as well as products of low quality.Several meth…     

Effects of the adenylate cyclase activator forskolin and its inactive derivative 1,9-dideoxyforskolin on insect cytochrome P-450 dependent steroid hydroxylase activity

The adenylate cyclase activator forskolin and its pharmacologically inactive derivative 1,9-dideoxyforskolin were found to inhibit in a dose-dependent fashion the ecdysone 20-monooxygenase activity associated with wandering stage larvae ofDrosophila melanogaster and fat body and midgut from last instar larvae of the tobacco hornworm,Manduca sexta. The concentrations of these labdane diterpenes required to elicit a 50% inhibition of the cytochrome P-450 dependent steroid hydroxylase activity in the insect tissues ranged from approximately 5×10^–6 to 5×10^–4 M.     

K_2PtCl_4与细胞色素C修饰体系研究

马心细胞色素C(以下简写为Cyt·C)与K_2PtCl_4的反应混合物在Sephadex G-75上分出4个组分,对应于Cyt·C寡聚体、三聚体、二聚体及单体,此结果与SDS聚丙烯酰胺凝胶电泳(以下简写为SDS-PAGE)测定的各组分的分子量相一致,这揭示了K_2PtCl_4与Cyt·C存在多位点修饰,而非如Kostic报道的Met-65为其唯一修饰位点,此结论通过分析K_2PtCl_4与His-33羧甲基化的Cyt·C修饰反应产物所证实,同时也和同样条件下游离His,Met与K_2PtCl_4的配位作用相吻合,对Cyt·C二聚体衍生物的还原电位、紫外-可见光谱以及二阶导数傅利叶变换红外光谱研究表明,血红素周围的电子环境仍然保持完整,但其二级结构有较大的扰动.