• 【氯苯诱导的大鼠肝中谷胱甘肽代谢异常对半胱氨酸水平的影响。】 复制标题 收藏 收藏
    DOI:10.3177/jnsv.31.69 复制DOI
    作者列表:Yoshida M,Hara I
    BACKGROUND & AIMS: :Effects of chlorobenzene-induced alteration in glutathione levels on cysteine metabolism in rat liver were investigated. Male Wistar rats were intraperitoneally injected with chlorobenzene (0.2, 0.5, 1.0 or 2.0 mmol/kg body weight). Both hepatic glutathione and cysteine levels were dose-dependently decreased by the chlorobenzene 6 h after the injection. However, at 24 h, the glutathione in the rats with chlorobenzene increased significantly as compared to that in the rats without chlorobenzene. Concomitant to the elevation in glutathione levels, hepatic glutathione synthesis activities were increased by the chlorobenzene by 68-111%. On the other hand, no significant difference between the rats with and without chlorobenzene was observed as regards cysteine levels at 24 h. Hepatic glutamate, glycine, methionine and serine levels were unaltered but hepatic taurine levels were significantly decreased by the chlorobenzene at both 6 and 24 h. Chlorobenzene administration had no effect on hepatic cystathionine synthase and cystathionase activities. These results indicate that a transient loss of hepatic glutathione, caused by the administration of chlorobenzene, resulted in an acceleration of glutathione synthesis and an increase of cysteine demand in the liver.
    背景与目标: :研究了氯苯诱导的谷胱甘肽水平改变对大鼠肝脏半胱氨酸代谢的影响。给雄性Wistar大鼠腹膜内注射氯苯(0.2、0.5、1.0或2.0mmol / kg体重)。注射后6小时,氯苯引起的肝谷胱甘肽和半胱氨酸水平均呈剂量依赖性下降。然而,在24小时时,与不含氯苯的大鼠相比,含氯苯的大鼠中的谷胱甘肽显着增加。伴随谷胱甘肽水平的升高,氯苯使肝谷胱甘肽合成活性提高了68-111%。另一方面,在有和没有氯苯的大鼠之间,在24小时的半胱氨酸水平上没有观察到显着差异。肝谷氨酸,甘氨酸,蛋氨酸和丝氨酸水平未改变,但在6和24 h时,氯苯可显着降低肝牛磺酸水平。施用氯苯对肝脏胱硫醚合酶和胱硫醚酶活性没有影响。这些结果表明,由于施用氯苯引起的肝谷胱甘肽的瞬时损失,导致谷胱甘肽合成的加速和肝脏中半胱氨酸需求的增加。
  • 【Gordonia sp。中脂质积累和体内酯形成的生理学表征。 KTR9。】 复制标题 收藏 收藏
    DOI:10.1007/s10295-012-1218-6 复制DOI
    作者列表:Eberly JO,Ringelberg DB,Indest KJ
    BACKGROUND & AIMS: :Previous work has demonstrated the feasibility of in vivo biodiesel synthesis in Escherichia coli, however, ethyl ester formation was dependent on an external fatty acid feedstock. In contrast to E. coli, actinomycetes may be ideal organisms for direct biodiesel synthesis because of their capacity to synthesize high levels of triacylglcerides (TAGs). In this study, we investigated the physiology and associated TAG accumulation along with the in vivo ability to catalyze ester formation from exogenous short chain alcohol sources in Gordonia sp. KTR9, a strain that possesses a large number of genes dedicated to fatty acid and lipid biosynthesis. Total lipid fatty acids content increased by 75 % and TAG content increased by 50 % under nitrogen starvation conditions in strain KTR9. Strain KTR9 tolerated the exogenous addition of up to 4 % methanol, 4 % ethanol and 2 % propanol in the media. Increasing alcohol concentrations resulted in a decrease in the degree of saturation of recovered fatty acid alcohol esters and a slight increase in the fatty acid chain length. A linear dose dependency in fatty alcohol ester synthesis was observed in the presence of 0.5-2 % methanol and ethanol compared to control KTR9 strains grown in the absence of alcohols. An inspection of the KTR9 genome revealed the presence of several putative wax ester synthase/acyl-coenzyme A : diacylglycerol acyltransferase (WS/DGAT) enzymes, encoded by atf gene homologs, that may catalyze the in vivo synthesis of fatty acid esters from short chain alcohols. Collectively, these results indicate that Gordonia sp. KTR9 may be a suitable actinomycete host strain for in vivo biodiesel synthesis.
    背景与目标: :先前的工作证明了在大肠杆菌中体内生物柴油合成的可行性,但是,乙酯的形成取决于外部脂肪酸原料。与大肠杆菌相反,放线菌可能是直接生物柴油合成的理想生物,因为它们能够合成高含量的三酰基甘油(TAGs)。在这项研究中,我们调查了生理和相关的TAG积累以及体内催化Gordonia sp。中外源短链醇源形成酯的能力。 KTR9,具有大量致力于脂肪酸和脂质生物合成的基因的菌株。在氮饥饿条件下,菌株KTR9的总脂质脂肪酸含量增加了75%,TAG含量增加了50%。菌株KTR9耐受培养基中外源添加多达4%的甲醇,4%的乙醇和2%的丙醇。醇浓度的增加导致回收的脂肪酸醇酯的饱和度降低,并且脂肪酸链长度略微增加。与在不存在醇的情况下生长的对照KTR9菌株相比,在存在0.5-2%的甲醇和乙醇的条件下观察到脂肪醇酯合成的线性剂量依赖性。对KTR9基因组的检查表明存在几种假定的蜡酯合酶/酰基辅酶A:二酰基甘油酰基转移酶(WS / DGAT)酶,这些酶由atf基因同源物编码,可能催化体内短链脂肪酸酯的合成酒精。总的来说,这些结果表明Gordonia sp。 KTR9可能是适合体内生物柴油合成的放线菌宿主菌株。
  • 【分析代谢网络以研究癌症代谢。】 复制标题 收藏 收藏
    DOI:10.1016/j.copbio.2012.11.001 复制DOI
    作者列表:Hiller K,Metallo CM
    BACKGROUND & AIMS: :Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.
    背景与目标: :癌症是细胞生长和存活不受控制的疾病,肿瘤会重编程生化途径来辅助这些过程。现在已经出现了在代谢的计算和生物分析表征中的新功能,从而有助于识别在特定癌症中出现的独特代谢依赖性。通过了解癌症的代谢表型作为其致癌特征的函数,可以将代谢工程应用于某些肿瘤的合成致死疗法的设计。此过程从准确测量代谢通量开始。在这里,我们回顾了量化途径活性的先进方法,并重点介绍了这些方法已发现潜在的治疗干预机会的具体例子。
  • 【在玉米芯酸水解产物和大豆油的混合培养基中,由Trichosporon dermatis组合进行“从头”和“从头”脂质发酵。】 复制标题 收藏 收藏
    DOI:10.1186/s13068-017-0835-8 复制DOI
    作者列表:Huang C,Luo MT,Chen XF,Qi GX,Xiong L,Lin XQ,Wang C,Li HL,Chen XD
    BACKGROUND & AIMS: BACKGROUND:Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways ("de novo" lipid fermentation and "ex novo" lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both "de novo" and "ex novo" lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. RESULTS:In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined "de novo" and "ex novo" lipid fermentation by oleaginous yeast Trichosporon dermatis. Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis. Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis. CONCLUSIONS:The present study proves the potential and possibility of combined "de novo" and "ex novo" lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.
    背景与目标: 背景:微生物油因其在能源,化工和食品工业中的重要作用而成为一种重要的生物产品。寻找合适的基材是其工业应用的关键问题之一。具有两种不同生物途径(“从头”脂质发酵和“从头”脂质发酵)的油脂性微生物均可利用亲水性和疏水性底物。迄今为止,大多数关于脂质发酵的研究主要集中在仅一种发酵途径上,并且很少同时进行“从头”和“从头”脂质发酵的工作。因此,不能同时实现两种脂质发酵的优点。
    结果:在这项研究中,玉米芯酸与大豆油的水解产物被用作混合培养基,用于油脂性酵母曲氏菌(Trichosporon dermatis)的“从头”和“从头”组合脂质发酵。皮肤癣菌可同时有效地利用培养基中的亲水性和疏水性底物(糖和大豆油)。比较了不同的发酵模式,分批模式最适合组合发酵。评估了豆油浓度,接种量和初始pH对脂质发酵的影响,并且20 g / L豆油,5%接种量和pH 6.0适于此生物工艺。通过该技术,可以修饰细胞外疏水性底物(大豆油)的脂质组成。尽管添加乳化剂对脂质的产生几乎没有有益作用,但它可以改变皮肤炎球菌的细胞内脂质组成。
    结论:本研究证明了“从头”和“从头”脂质发酵相结合的潜力和可能性。该技术可以利用亲水和疏水的可持续生物资源来生产脂质原料,以生产生物柴油或其他基于脂质的化合物,并处理某些特殊废物,例如含油废水。
  • 【竹制饮食中的多种饮食对于大熊猫(Ailuropoda melanoleuca)的代谢和健康很重要。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-017-03216-8 复制DOI
    作者列表:Wang H,Zhong H,Hou R,Ayala J,Liu G,Yuan S,Yan Z,Zhang W,Liu Y,Cai K,Cai Z,Huang H,Zhang Z,Wu
    BACKGROUND & AIMS: :The aim of this study was to determine the metabolic response in giant pandas (Ailuropoda melanoleuca) to the consumption of certain parts of bamboo above ground growth. Giant pandas were provisioned with three species of bamboo: Phyllostachys bissetii, of which they only consume the culm (culm group); Bashania fargesii, of which they only consume the leaves (leaf group); and Qiongzhuea opienensis, of which they only consume the shoots (shoot group). The "culm" group absorbed the highest amount of calories and fiber, but was in short energy supply (depressed tricarboxylic acid cycle activity), and high fiber level diet might reduce the digestibility of protein. The "culm" and "leaf" groups absorbed less protein, and had a lower rate of body mass growth than the "shoot" group. Digestion of fiber requires energy input and yields low caloric extraction from the culm and leaf, and protein intake is important for increasing body mass. However, long-term consumption of shoots may have a potentially negative effect on the health because of high protein composition. Therefore, a balanced diet consisting of diverse plant parts of bamboo is important for the overall metabolic function and health of captive giant pandas.
    背景与目标: :这项研究的目的是确定大熊猫(Ailuropoda melanoleuca)对高于地面生长的竹子某些部位的消耗的代谢反应。大熊猫被提供了三种竹子:毛竹楠(Phyllostachys bissetii),它们只食用茎秆(茎秆组)。 shan藜(Bashania fargesii),只食用叶子(叶组);和琼竹opienensis,他们只消耗芽(拍摄组)。 “茎”类吸收了最高量的卡路里和纤维,但能量供应不足(三羧酸循环活性降低),高纤维饮食可能会降低蛋白质的消化率。 “茎”和“叶”组比“茎”组吸收更少的蛋白质,并且具有较低的体重增长速度。纤维的消化需要能量输入,并且从茎和叶中产生的热量低,蛋白质的摄入对于增加体重很重要。但是,由于高蛋白质组成,长期食用芽可能对健康产生潜在的负面影响。因此,由竹子的不同植物部分组成的均衡饮食对于圈养大熊猫的整体代谢功能和健康至关重要。
  • 【线粒体靶向视蛋白的线粒体代谢和Ca2信号的光遗传学控制。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1703623114 复制DOI
    作者列表:Tkatch T,Greotti E,Baranauskas G,Pendin D,Roy S,Nita LI,Wettmarshausen J,Prigge M,Yizhar O,Shirihai OS,Fishman D,Hershfinkel M,Fleidervish IA,Perocchi F,Pozzan T,Sekler I
    BACKGROUND & AIMS: :Key mitochondrial functions such as ATP production, Ca2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH+) across the inner membrane. Although several drugs can modulate ΔμH+, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψm) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca2+ dynamics, and respiratory metabolism. By directly modulating Δψm, the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.
    背景与目标: :线粒体的关键功能(例如ATP的产生,Ca2的吸收和释放以及底物的积累)取决于跨内膜的质子电化学梯度(ΔμH)。尽管几种药物可以调节ΔμH,但其作用几乎不可逆,并且缺乏细胞特异性和空间分辨率。尽管通道视紫红质被广泛用于调节可兴奋细胞的质膜电位,但线粒体迄今仍未进行光遗传学控制。在这里,我们描述了一种基于选择性具有选择性功能的通道视紫红质靶向完整细胞内部线粒体膜的光代谢构建物的工具包。我们表明,我们的策略能够实现线粒体膜电位(Δψm)的光依赖性控制以及耦合的线粒体功能,例如通过氧化磷酸化,Ca2动力学和呼吸代谢的ATP合成。通过直接调节Δψm,靶向线粒体的视蛋白被用于控制复杂的生理过程,例如心肌细胞的自发搏动和胰腺β细胞的葡萄糖依赖性ATP增加。此外,我们的光代谢工具允许调节单个细胞和定义的细胞区域中的线粒体功能。
  • 【人参皂苷对胆固醇7α-羟化酶表达的影响增加,但胆汁盐输出泵的影响不大,这与胆固醇的代谢有关。】 复制标题 收藏 收藏
    DOI:10.1007/s11418-012-0713-4 复制DOI
    作者列表:Kawase A,Yamada A,Gamou Y,Tahara C,Takeshita F,Murata K,Matsuda H,Samukawa K,Iwaki M
    BACKGROUND & AIMS: :An extract from red ginseng [steamed and dried roots of Panax ginseng C.A. Meyer (RGE)] has been shown to have various actions on physiological functions. The mechanisms by which RGE promotes cholesterol metabolism in the liver are unclear, but RGE decreases the plasma levels of cholesterol. We investigated whether RGE affected the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed the upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with RGE. Treatment with RGE exhibited decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol compared with hypercholesterolemia without RGE. In-vitro studies also showed the upregulation of CYP7A1 mRNA and protein levels by the addition of RGE to rat primary hepatocytes. The mRNA levels of BSEP exhibited few changes. The sustained levels of the liver X receptor (LXR) in vivo and the increased levels of LXR in vitro on RGE treatment could be involved in the upregulation of CYP7A1. To clarify the effects of 11 ginsenosides including RGE on the mRNA levels of CYP7A1 and BSEP, we performed in-vitro experiments using rat primary hepatocytes. The ginsenosides Ro, Rg3, Re, Rg1, and Rg2 exhibited increased mRNA levels of CYP7A1. These results suggest that several ginsenosides including RGE promoted cholesterol metabolism due to upregulation of CYP7A1.
    背景与目标: :红参的提取物[人参C.A.的蒸干后的根。 Meyer(RGE)]已显示对生理功能有多种作用。 RGE促进肝脏中胆固醇代谢的机制尚不清楚,但RGE会降低血浆中的胆固醇水平。我们调查了RGE是否会影响高胆固醇血症大鼠和大鼠原代肝细胞肝脏中胆固醇代谢相关蛋白(如细胞色素P450(CYP)7A1和胆盐输出泵(BSEP))的mRNA表达。体内研究显示,用RGE治疗的高胆固醇血症大鼠中CYP7A1 mRNA的上调。与没有RGE的高胆固醇血症相比,RGE治疗显示低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比率降低。体外研究还显示,通过向大鼠原代肝细胞中添加RGE,CYP7A1 mRNA和蛋白水平上调。 BSEP的mRNA水平几乎没有变化。体内肝脏X受体(LXR)的持续水平和RGE治疗后体外LXR的水平升高可能与CYP7A1的上调有关。为了阐明包括RGE在内的11种人参皂苷对CYP7A1和BSEP mRNA水平的影响,我们使用大鼠原代肝细胞进行了体外实验。人参皂甙Ro,Rg3,Re,Rg1和Rg2的CYP7A1 mRNA水平升高。这些结果表明,几种人参皂苷(包括RGE)由于CYP7A1的上调而促进了胆固醇的代谢。
  • 【叶绿体超微结构和膜脂质组成与菠菜,常春藤和云杉叶片获得的不同抗冻性程度的相关性。】 复制标题 收藏 收藏
    DOI:10.1016/S0176-1617(84)80015-2 复制DOI
    作者列表:Senser M,Beck E
    BACKGROUND & AIMS: :The leaves of «moderately hardy» (spinach), «very hardy» (ivy) and «extremely hardy» (spruce) plants [classification according to Levitt {1980)] show characteristic differences with respect to changes in membrane lipid composition and chloroplast ultrastructure which are correlated with the degree of the frost resistance achieved by each type of tissue during adaptation to sub-zero temperatures. Spinach leaves showed no increase in their total lipid content upon frost hardening. On the contrary, the amount of galactolipids decreased considerably, whereas that of phospholipids only slightly increased. No shift from the saturated palmitic acid to the three-fold unsaturated linolenic acid was observed. The membrane lipid content of ivy leaves and spruce needles increased to a similar extent during frost hardening. However, in contrast to spruce needles, a distinct preferential accumulation of the phospholipids was observed in ivy leaves, resulting in an increased PL/GL ratio. A considerable shift from saturated (palmitic) to unsaturated fatty acids was detected in both plants, due mainly to an increase in the proportion of linoleic acid in ivy and of linolenic acid in spruce. In spite of the considerable increase in lipid content, no increase in chloroplast number per cell could be detected in ivy leaves, although the length of the thylakoids was nearly doubled and the plastids appeared to be in a division stage: however, no real division could ever be observed. On the contrary, an increase in the number of chloroplasts and mitochondria was observed in spruce needles. Membrane augmentation became further evident by the many large invaginations of the chloroplast envelope formed when the frost-hardened leaves of ivy or spruce were exposed to sub-zero temperatures which they could just survive.
    背景与目标: :“中等硬度”(菠菜),“极度坚硬”(ivy)和“极度坚硬”(云杉)植物的叶子[根据Levitt(1980)分类)在膜脂成分和叶绿体变化方面表现出特征差异超微结构,与适应零度以下温度时每种组织的抗冻性程度有关。霜冻硬化后,菠菜叶的总脂质含量没有增加。相反,半乳糖脂的量显着减少,而磷脂的量仅略有增加。没有观察到从饱和的棕榈酸到三倍的不饱和亚麻酸的转变。在霜冻硬化过程中,常春藤叶和云杉针的膜脂含量增加了相似的程度。然而,与云杉针头相反,在常春藤叶中观察到磷脂的明显优先积累,从而导致PL / GL比增加。在这两种植物中均检测到从饱和(棕榈酸)到不饱和脂肪酸的显着变化,这主要是由于常春藤中亚油酸和云杉中亚麻酸的比例增加。尽管脂质含量显着增加,但常春藤叶中未检测到每细胞的叶绿体数量增加,尽管类囊体的长度几乎增加了一倍,质体似乎处于分裂阶段:但是,不能进行真正的分裂曾经被观察到。相反,在云杉针头中观察到叶绿体和线粒体数量增加。当常春藤或云杉的冻干叶子暴露于零度以下的温度下就可以生存时,叶绿体包膜的许多大的浸入使膜的增强变得更加明显。
  • 【肥胖男性中大剂量白藜芦醇的补充:一项由研究人员发起,随机,安慰剂对照的底物代谢,胰岛素敏感性和身体成分的临床试验。】 复制标题 收藏 收藏
    DOI:10.2337/db12-0975 复制DOI
    作者列表:Poulsen MM,Vestergaard PF,Clasen BF,Radko Y,Christensen LP,Stødkilde-Jørgensen H,Møller N,Jessen N,Pedersen SB,Jørgensen JO
    BACKGROUND & AIMS: :Obesity, diabetes, hypertension, and hyperlipidemia constitute risk factors for morbidity and premature mortality. Based on animal and in vitro studies, resveratrol reverts these risk factors via stimulation of silent mating type information regulation 2 homolog 1 (SIRT1), but data in human subjects are scarce. The objective of this study was to examine the metabolic effects of high-dose resveratrol in obese human subjects. In a randomized, placebo-controlled, double-blinded, and parallel-group design, 24 obese but otherwise healthy men were randomly assigned to 4 weeks of resveratrol or placebo treatment. Extensive metabolic examinations including assessment of glucose turnover and insulin sensitivity (hyperinsulinemic euglycemic clamp) were performed before and after the treatment. Insulin sensitivity, the primary outcome measure, deteriorated insignificantly in both groups. Endogenous glucose production and the turnover and oxidation rates of glucose remained unchanged. Resveratrol supplementation also had no effect on blood pressure; resting energy expenditure; oxidation rates of lipid; ectopic or visceral fat content; or inflammatory and metabolic biomarkers. The lack of effect disagrees with persuasive data obtained from rodent models and raises doubt about the justification of resveratrol as a human nutritional supplement in metabolic disorders.
    背景与目标: 肥胖,糖尿病,高血压和高脂血症是发病率和过早死亡的危险因素。根据动物和体外研究,白藜芦醇通过刺激无声交配类型信息调节2同源物1(SIRT1)来逆转这些危险因素,但人类受试者的数据却很少。这项研究的目的是检查高剂量白藜芦醇在肥胖人类受试者中的代谢作用。在随机,安慰剂对照,双盲和平行组设计中,将24名肥胖但其他方面健康的男性随机分配到白藜芦醇或安慰剂治疗4周。在治疗之前和之后进行了广泛的代谢检查,包括评估葡萄糖更新和胰岛素敏感性(高胰岛素正常血糖钳夹)。两组的主要结果指标胰岛素敏感性均无显着性恶化。内源性葡萄糖的产生以及葡萄糖的周转率和氧化率保持不变。补充白藜芦醇对血压也没有影响。静态能量消耗;脂质的氧化速率;异位或内脏脂肪含量;或炎症和代谢生物标志物。缺乏效果与从啮齿动物模型获得的有说服力的数据不同,并引起人们对白藜芦醇作为代谢障碍中人类营养补充剂的合理性的怀疑。
  • 【植物化学代谢和处置的个体差异。】 复制标题 收藏 收藏
    DOI:10.1016/j.semcancer.2007.05.003 复制DOI
    作者列表:Lampe JW,Chang JL
    BACKGROUND & AIMS: :Many phytochemicals, the bioactive nonnutrient compounds found in plant foods, possess biologic effects associated with reduced risk of various diseases such as cancer. Genetic variation in pathways affecting absorption, metabolism, and distribution of phytochemicals is likely to influence exposure at the tissue level, thus modifying disease risk in individuals. Few studies have examined these gene-phytochemical interactions in humans. In this review, we discuss the sources of variation in metabolism and disposition of phytochemicals, and focus on two aspects of phytochemical handling that have received some attention: the impact of intestinal bacteria and genetically polymorphic phase II, conjugating enzymes.
    背景与目标: :许多植物性化学物质是植物性食品中发现的具有生物活性的非营养性化合物,具有与降低各种疾病(如癌症)风险相关的生物作用。影响植物化学物质吸收,代谢和分布的途径中的遗传变异可能会影响组织水平的暴露,从而改变个体的疾病风险。很少有研究检查人类中的这些基因-植物化学相互作用。在这篇综述中,我们讨论了植物化学物质代谢和处置变化的来源,并着重研究了受到关注的植物化学物质处理的两个方面:肠道细菌和遗传多态性II期的影响,结合酶。
  • 【包括HDL及其脂质过氧化产物在内的氧化脂蛋白抑制THP-1人巨噬细胞分泌TNF-α。】 复制标题 收藏 收藏
    DOI:10.1016/s0891-5849(97)00061-0 复制DOI
    作者列表:Girona J,La Ville AE,Heras M,Olivé S,Masana L
    BACKGROUND & AIMS: It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

    背景与目标: 已经确定氧化的LDL(ox-LDL)可以通过减少肿瘤坏死因子α(TNF-αm-RNA)来调节巨噬细胞的细胞因子分泌。但是,对氧化的高密度脂蛋白的作用知之甚少(ox-HDL)。这项研究报告了与ox-LDL和某些氧化产物(氢过氧化物和醛类)相比,ox-HDL亚组分2和3(ox-HDL2,ox-HDL3)对TNF分泌的影响THP-1人单核细胞衍生的α-α体外,将HDL2,HDL3和LDL用10 microM Cu氧化12 h和/或24 h,将天然和氧化的HDL和LDL与有或没有LPS的巨噬细胞孵育24 h (10 ng / ml),然后在培养基中测量TNF-α的分泌,脂质过氧化氢和非极性醛也与细胞一起孵育2小时,然后更换培养基,再过22 h后测量TNF-α的分泌ox-HDL2对TNF-α的抑制作用(p < .05),在存在和不存在LPS的情况下观察到THP-1巨噬细胞的ox-HDL3(p <.05)和ox-LDL(p <.05)。与ox-HDL孵育12小时和24小时后,这种抑制作用保持不变。亚油酸的氢过氧化物不会改变细胞的TNF-α分泌,而分析的八种醛中的五种(2,4-庚二烯醛,己醛,2-壬烯醛,2-辛烯醛,2,4-癸二烯醛)抑制TNF-α分泌(p <.05)。这些发现表明,ox-HDL及其某些脂质过氧化产物在巨噬细胞对炎症反应的调节中起着作用,正如以前对ox-LDL所观察到的一样。

  • 【有机锡和有机铅化合物与模型脂质膜的疏水和亲水相互作用的作用。】 复制标题 收藏 收藏
    DOI:10.1515/znc-1997-3-412 复制DOI
    作者列表:Gabrielska J,Sarapuk J,Przestalski S
    BACKGROUND & AIMS: The present study was conducted to clarify the mechanism of toxicity of organic compounds using lipid model membranes (liposomes and planar lipid membranes). The compounds studied were trialkyltin and trialkyllead chlorides, dialkyltin dichlorides and some inorganic forms of those metals. Two different (anionic and cationic) detergents were also used in the experiments to change the surface properties of liposomes. As a measure of interaction between the compounds studied and model membranes were the release of liposome bound praseodymium and the change in stability of planar membranes under the influence of those compounds. On the basis of the results obtained it was postulated that the mechanism of interaction between tin- and leadorganics and model lipid membranes is a combination of different factors featuring interacting sides. The most important properties determining the behaviour of organic compounds in the interaction were lipophilicity and polarity of different parts of the organics and the steric arrangement they can take in the medium. On the other hand, the surface potential of the lipid bilayer and the environment of the lipid molecules, that play a significant role in the availability of the lipid bilayer to the organics, were important factors in the interaction.

    背景与目标: 进行本研究以阐明使用脂质模型膜(脂质体和平面脂质膜)的有机化合物的毒性机理。所研究的化合物为三烷基锡和三烷基氯化铅,二烷基二氯化锡和这些金属的某些无机形式。实验中还使用了两种不同的(阴离子和阳离子)去污剂来改变脂质体的表面性质。脂质体结合的ody的释放以及在这些化合物的影响下平面膜稳定性的变化是衡量所研究化合物与模型膜之间相互作用的一种量度。根据获得的结果,假设锡和铅有机物与模型脂质膜之间的相互作用机理是具有相互作用侧的不同因素的组合。决定有机化合物在相互作用中的行为的最重要特性是亲脂性和有机物不同部分的极性以及它们在介质中可采取的空间排列。另一方面,脂质双层的表面电势和脂质分子的环境在脂质双层对有机物的利用中起着重要作用,是相互作用的重要因素。

  • 【糖酵解代谢赋予了对全反式维甲酸和三氧化二砷诱导的HL60rho0细胞凋亡的抵抗力。】 复制标题 收藏 收藏
    DOI:10.1016/j.leukres.2007.04.014 复制DOI
    作者列表:Herst PM,Hesketh EL,Ritchie DS,Berridge MV
    BACKGROUND & AIMS: :Glycolytic cancers are resistant to many forms of chemotherapy and some respond poorly to differentiation therapies. Here, we investigate the effects of exposure to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) on differentiation and cell survival in the human leukemia cell line, HL60 and its mitochondrial gene knockout mutant, HL60rho0. Glycolytic HL60rho0 cells exposed to single and combined treatments expressed less CD15, in most cases, but produced a stronger respiratory burst than parental HL60 cells. HL60rho0 cells were also significantly more resistant to apoptosis after combined ATO+ATRA treatment compared with HL60 cells, and this was associated with failure to upregulate Fas expression.
    背景与目标: :糖酵解性癌症对多种形式的化学疗法都有抵抗力,有些对分化疗法反应差。在这里,我们研究了暴露于全反式维甲酸(ATRA)和三氧化二砷(ATO)对人白血病细胞系HL60及其线粒体基因敲除突变体HL60rho0的分化和细胞存活的影响。在大多数情况下,暴露于单一治疗和联合治疗的糖酵解HL60rho0细胞表达的CD15较少,但与亲代HL60细胞相比,产生的呼吸爆发更强。 HL60rho0细胞在ATO ATRA联合治疗后对凋亡的抵抗力也比HL60细胞高得多,这与无法上调Fas表达有关。
  • 【神经性厌食症和情感障碍的大脑葡萄糖代谢:体重减轻或抑郁症状的影响。】 复制标题 收藏 收藏
    DOI:10.1016/s0925-4927(97)02971-5 复制DOI
    作者列表:Delvenne V,Goldman S,De Maertelaer V,Wikler D,Damhaut P,Lotstra F
    BACKGROUND & AIMS: :Relationships between eating and affective disorders remain complex and unclear. Brain glucose metabolism of anorectic patients has been demonstrated to be reduced both globally and regionally, with a particular relative hypometabolism in the parietal cortex. To explore the possible influence of weight loss or depressive symptomatology on brain metabolism, we studied age- and sex-matched low-weight anorectic and depressed patients, normal-weight depressed patients, and healthy volunteers. Absolute global and regional glucose activity levels were reduced in low-weight patients, with the lowest values being found for anorectic patients. In relative values, anorectic patients showed a significant parietal hypometabolism in comparison to control subjects while they had higher metabolism in the caudate nuclei when compared with the other groups. Absolute hypometabolism of glucose seems to be a consequence of low weight as it was found in both low-weight anorectic and low-weight depressive patients. In addition, absolute glucose values were significantly correlated with body mass index in all subjects. Future positron emission tomographic studies in psychiatric patients should control for alimentary parameters.
    背景与目标: 饮食和情感障碍之间的关系仍然复杂且不清楚。厌食症患者的脑葡萄糖代谢已被证实在全球和区域均降低,顶叶皮层中存在特定的相对低代谢。为了探索减肥或抑郁症状对脑代谢的可能影响,我们研究了年龄和性别相匹配的低体重厌食症和抑郁症患者,正常体重的抑郁症患者以及健康志愿者。低体重患者的全球和区域绝对葡萄糖活性水平降低,而厌食患者的葡萄糖水平最低。在相对价值方面,与对照组相比,厌食患者的顶叶代谢明显降低,而尾核中的新陈代谢较其他组更高。葡萄糖的绝对低代谢似乎是低体重的结果,因为它在低体重厌食症患者和低体重抑郁症患者中均被发现。另外,在所有受试者中,绝对葡萄糖值与体重指数显着相关。未来精神病患者的正电子发射断层扫描研究应控制饮食参数。
  • 【长期缺氧对海湾金枪鱼,大底Fund中碳水化合物代谢酶的影响。】 复制标题 收藏 收藏
    DOI:10.1242/jeb.02437 复制DOI
    作者列表:Martínez ML,Landry C,Boehm R,Manning S,Cheek AO,Rees BB
    BACKGROUND & AIMS: :The goal of the current study was to generate a comprehensive, multi-tissue perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3 mg l(-1) dissolved oxygen (approximately 3.6 kPa) for 4 weeks, after which maximal activities were measured for all glycolytic enzymes in four tissues (white skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen metabolism (in muscle and liver) and gluconeogenesis (in liver). The specific activities of enzymes of glycolysis and glycogen metabolism were strongly suppressed by hypoxia in white skeletal muscle, which may reflect decreased energy demand in this tissue during chronic hypoxia. In contrast, several enzyme specific activities were higher in liver tissue after hypoxic exposure, suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure affected fewer enzymes in heart and brain than in skeletal muscle and liver, and the changes were smaller in magnitude, perhaps due to preferential perfusion of heart and brain during hypoxia. The specific activities of some gluconeogenic enzymes increased in liver during long-term hypoxic exposure, which may be coupled to increased protein catabolism in skeletal muscle. These results demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme activities respond in a tissue-specific fashion reflecting the balance of energetic demands, metabolic role and oxygen supply of particular tissues. Furthermore, within glycolysis, the effects of hypoxia varied among enzymes, rather than being uniformly distributed among pathway enzymes.
    背景与目标: :本研究的目的是就海湾缺氧大鱼眼底大堡礁中长期低氧暴露对碳水化合物代谢的影响产生一个综合的,多组织的观点。将鱼置于约1.3 mg l(-1)的溶解氧下(约3.6 kPa)保持4周,此后还测量了四个组织(白骨骼肌,肝,心脏和脑)中所有糖酵解酶的最大活性至于糖原代谢(在肌肉和肝脏中)和糖异生(在肝脏中)的酶。白色骨骼肌中的缺氧强烈抑制了糖酵解酶和糖原代谢酶的比活,这可能反映了慢性缺氧时该组织能量需求的减少。相反,低氧暴露后肝组织中几种酶的比活较高,表明碳水化合物代谢的能力增强。低氧暴露对心脏和大脑的酶影响少于骨骼肌和肝脏,并且变化幅度较小,这可能是由于缺氧期间心脏和大脑的优先灌注所致。长期低氧暴露期间肝脏中某些糖异生酶的比活性增加,这可能与骨骼肌中的蛋白质分解代谢增加有关。这些结果表明,当完整的鱼类长时间缺氧时,酶活性以组织特异性方式响应,反映出特定组织的能量需求,代谢作用和氧气供应之间的平衡。此外,在糖酵解中,缺氧的影响在酶之间变化,而不是在途径酶之间均匀分布。

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