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131.
Kelem Kassahun Pei Hu Mark P. Grillo Margaret R. Davis Lixia Jin Thomas A. Baillie 《Chemico-biological interactions》1994,90(3):253-275
The ability of 2-n-propyl-4-pentenoic acid (Δ4-VPA) and 2-n-propyl-2(E)-pentenoic acid ([E]-Δ2-VPA), two unsaturated metabolites of valproic acid (VPA), to form reactive intermediates, deplete hepatic glutathione (GSH) and cause accumulation of liver triglycerides was investigated in the rat. With the aid of ionspray liquid chromatography-tandem mass spectrometry (LC-MS/MS), three GSH adducts were detected in the bile of Δ4-VPA-treated animals and were identified as 4-hydroxy-5-glutathion-S-yl-VPA-γ-lactone, 5-glutathion-S-yl-(E)-Δ3-VPA and 3-oxo-5-glutathion-S-yl-VPA. A fourth conjugate was identified tentatively as 4-glutathion-S-yl-5-hydroxy-VPA. Quantitative analysis of the corresponding N-acetylcysteine (NAC) conjugates in urine indicated that metabolism of Δ4-VPA via the GSH-dependent pathways accounted for approximately 20% of an acute dose (100 mg kg−1 i.p.). In contrast, when rats were given an equivalent dose of (E)-Δ2-VPA, only one GSH adduct (5-glutathion-S-yl-(E)-Δ3-VPA) was detected at low concentrations in bile. In vitro experiments with rat liver mitochondria demonstrated that Δ4-VPA undergoes coenzyme A- and ATP-dependent metabolic activation in this organelle via the β-oxidation pathway to intermediates which bind covalently to proteins. When liver homogenates and hepatic mitochondria from rats injected with Δ4-VPA, (E)-Δ2-VPA or VPA were analyzed for GSH content, it was found that only Δ4-VPA depleted GSH pools significantly. Treatment of rats with Δ4-VPA and (to a lesser extent) VPA led to an accumulation of liver triglycerides, whereas (E)-Δ2-VPA had no measurable effect. It is concluded that Δ4-VPA undergoes metabolic activation by both microsomal cytochrome P-450-dependent and mitochondrial coenzyme A-dependent processes, and that the resulting electrophilic intermediates, which are trapped in part by GSH, may mediate the hepatotoxic effects of this compound. In contrast, (E)-Δ2-VPA is not transformed to any appreciable extent to reactive metabolites, which thus accounts for the apparent lack of hepatotoxicity of this positional isomer in the rat. 相似文献
132.
Repeated polyketide synthase modules involved in the biosynthesis of a heptaene macrolide by Streptomyces sp. FR-008 总被引:4,自引:2,他引:2
Zhihao Hu Kai Bao Xiufen Zhou Qi Zhou David A. Hopwood Tobias Kieser Zixln Deng 《Molecular microbiology》1994,14(1):163-172
Genes for biosynthesis of a Streptomyces sp. FR-008 heptaene macrolide antibiotic with antifungal and mosquito larvicidal activity were cloned in Escherichia coli using heterologous DNA probes. The cloned genes were implicated in heptaene biosynthiesis by gene replacement. The FR-008 antibiotic contains a 38-membered, poiyketide-derived macrolide ring. Southern hybridization using probes encoding domains of the type i modular erythromycin polyketide synthase (PKS) showed that the Streptomyces sp. FR-008 PKS gene cluster contains repeated sequences spanning c. 105 kb of contiguous DNA; assuming c. 5 kb for each PKS module, this is in striking agreement with the expectation for the 21-step condensation process required for synthesis of the FR-008 carbon chain. The methods developed for transformation and gene replacement in Streptomyces sp. FR-008 make it possible to genetically manipulate polyene macrolide production, and may later lead to the biosynthesis of novel polyene macrolides. 相似文献
133.
Summary A recombinant baculovirus (BmNPV-pk2) was constructed by inserting the human pro-urokinase(pro-UK) cDNA into the genome of baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) adjacent to the strong polyhedrin promoter. The recombinant virus replicated in silkworm larvae, which synthesized 30g pro-UK/ml in the haemolymph within 4 days post-infection. Purification to near homogeneity was accomplished by fractional precipitation with ammonium sulphate and immunoaffinity chromatography with an overall yield of 23% and a specific activity of 100,000IU/mg in fibrin plate assay. This purified product was comprised of a single chain protein with approximately Mr. 50kDa as determined by SDS-PAGE gel. The N-Terminal amino acids sequence revealed that the secretion signal of pro-UK was correctly processed. 相似文献
134.
对废水淤泥的厌氧消化处理过程进行了研究.提出了一种基于神经网络的非模型控制方法。多变量控制系统的操作变量为供热量和进水量.被控变量为消化温度和消化污泥排出浓度。证明了控制算法的收敛性。讨论了控制系统的稳定性。仿真结果证实了非模型控制方法的有效性。该方法无需对象的模型.为复杂生化过程的控制提供了一种新途径。 相似文献
135.
影响大肠杆菌中外源基因表达的因素 总被引:41,自引:1,他引:40
大肠杆菌已经被广泛地应用于表达各种外源基因,但是,不同的外源基因在表达效率上却有很大的差异,文章综述了影响大肠杆菌中外源基因表达的因素,这将有助于认识大肠杆菌中外源基因表达的规律,以便采取有效的方法提高外源基因在大肠杆菌中的表达效率. 相似文献
136.
Activation of recombinant trp by thapsigargin in Sf9 insect cells 总被引:12,自引:0,他引:12
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140.
油松鳞叶中细胞核穿壁现象的初步研究 总被引:1,自引:0,他引:1
利用薄切片和超薄切片技术对油松衰老鳞叶中细胞核穿壁运动进行了观察研究。首次,细胞核内的染色质逐渐收缩集中,形成染色深的球状体,以后,细胞核逐渐与细胞壁接近。接着紧贴细胞壁的细胞核通过细胞壁上的通道或胞间连丝转移到相邻的细胞内,此外,还发现有多种其它的转移方式存在。研究结果表明细胞核的穿壁运动现象同时存在于连子植物和裸植物中,电镜观察进一步证明细胞壁道在细胞核穿壁之前已形成。 相似文献