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91.
92.
目的:观察体外培养的Burkit淋巴瘤(Raji)细胞在氧化应激条件下细胞内葡萄糖-6-磷酸脱氢酶(G6PD)对还原型谷胱甘肽(GSH)水平的影响。方法:体外培养Raji细胞,分别在G6PD活性被抑制及不抑制的情况下,检测细胞在酚嗪甲酸硫酯(PMS)作用后60min及360min时G6PD、谷胱甘肽还原酶(GR)、谷胱甘肽过氧化物酶(GPx)活性及GSH水平。结果:在PMS作用下,Raji细胞内GSH水平在60min时显著下降(P〈0.01)而360min时可上升至对照组水平,G6PD及GPx活性持续显著升高(P〈0.01)而GR活性在360min时有显著升高(P〈0.01);使用脱氢表雄酮(DHEA)抑制G6PD活性后,Raji细胞再在PMS作用下,细胞内各指标与PMS处理组比较,GSH水平显著降低(P〈0.01),GPx活性在60min时显著增高(P〈0.05)而GR活性在360min时显著降低(P〈0.01)。结论:细胞在氧化应激条件下G6PD可能是Raji细胞内影响GSH水平的一个关键因子,对维持胞内GSH水平起重要的调节作用。  相似文献   
93.
Apoptosis and necrosis are two forms of cell death that can occur in response to various agents and oxidative damage. In addition to necrosis, apoptosis contributes to muscle fiber loss in various muscular dystrophies as well participates in the exudative diathesis in chicken, pathology caused by dietary deficiency of vitamin E and selenium, which affects muscle tissue. We have used chicken skeletal muscle cells and bovine fibroblasts to study molecular events involved in the cell death induced by oxidative stress and apoptotic agents. The effect of vitamin E on cell death induced by oxidants was also investigated. Treatment of cells with anti-Fas antibody (50 to 400 ng/mL), staurosporine (0.1 to 100 microM) and TNF-alpha (10 and 50 ng/mL) resulted in a little loss of Trypan blue exclusion ability. Those stimuli conducted cells to apoptosis detected by an enhancement in caspase activity upon fluorogenic substrates but this activity was not fully blocked by the caspase inhibitor Z-VAD-fmk. Oxidative stress induced by menadione (10, 100 and 250 muM) promoted a significant reduction in cell viability (10%, 20% and 35% for fibroblasts; 20%, 30% and 75% for muscle cells, respectively) and caused an increase in caspase activity and DNA fragmentation. H2O2 also promoted apoptosis verified by caspase activation and DNA fragmentation, but in higher doses induced necrosis. Vitamin E protected cells from death induced by low doses of oxidants. Although it was ineffective in reducing caspase activity in fibroblasts, this vitamin diminished the enzyme activity in muscle cells. These data suggested that oxidative stress could activate apoptotic mechanisms; however the mode of cell death will depend on the intensity and duration of the stimulus, and on the antioxidant status of the cells.  相似文献   
94.
Pyrrolidinedithiocarbamate (PDTC) is a metal chelating compound, which exerts both pro-apoptotic effect and pro-oxidant activity on many cells. Our objective was to investigate whether PDTC was able to interfere with apoptotic process in leukemic and normal bone marrow CD34+ cells. Since hematopoietic growth factors stimulate growth and differentiation and prevent apoptosis, we therefore studied the effect of growth factors pretreatment, such as interleukin-3 and granulocyte-macrophage colony stimulating factor, in human myeloid CD34+ cells to evaluate whether they protect the cells from the apoptotic action of PDTC.We revealed that PDTC exerted an apoptotic effect in leukemic CD34+ cells. This effect was dependent on the ability of this compound to generate the oxidation of cellular glutathion to its disulphide and consequently to induce an intracellular oxidative stress. Hematopoietic growth factors did not protect cells from apoptosis induced by previous treatment with PDTC. The ability of PDTC to induce apoptosis was restricted to acute myelogenous leukaemia CD34+ cells, since normal CD34+ cells were insensitive to the pro-oxidant effect of PDTC.These findings imply that normal cells are equipped with mechanisms by which they respond differently to PDTC effects with respect to leukemic cells.  相似文献   
95.
不同耐铝型杉木幼苗叶片抗氧化系统对铝胁迫的响应特征   总被引:2,自引:0,他引:2  
为探讨铝胁迫对杉木抗坏血酸-谷胱甘肽(AsA-GSH)循环的影响,明确AsA-GSH循环在杉木耐铝性中的作用,以耐铝(YX26)和铝敏感型(YX5)杉木家系为材料,分析了铝胁迫对不同耐铝型杉木叶片氧化损伤、抗氧化酶活性和AsA-GSH循环系统的影响。结果表明:(1)铝胁迫显著增加杉木叶片丙二醛(MDA)含量,而且YX5叶片中MDA含量增幅显著大于YX26。(2)铝胁迫不同程度增加了2个杉木家系叶片过氧化物酶(POD)、抗坏血酸过氧化物酶(APX)和单脱氢抗坏血酸还原酶(MDAR)活性以及抗坏血酸(AsA)、脱氢抗坏血酸(DHA)、还原型谷胱甘肽(GSH)和氧化型谷胱甘肽(GSSG)含量,而且除AsA含量外,铝胁迫下YX26中上述酶活性和非酶性抗氧化剂含量的增幅均大于YX5。(3)铝胁迫下YX5叶片中过氧化氢酶(CAT)和脱氢抗坏血酸还原酶(DHAR)的活性受到显著抑制,而YX26中这两个酶的活性却有所增加,且YX26中的DHAR活性显著高于对照。(4)铝胁迫抑制了2个杉木家系超氧化物歧化酶(SOD)活性,但YX26中SOD活性的降幅小于YX5。研究认为,铝胁迫下通过维持AsA-GSH循环酶活性和非酶性抗氧化系统的高效运转,增强自身活性氧清除能力是耐铝型杉木家系具有较强铝耐能力的生理基础。  相似文献   
96.
We present a comprehensive in vitro approach to assessing metabolism-mediated hepatotoxicity using male Sprague–Dawley rat liver slices incubated with the well characterized hepatotoxicant, precocene I, and inhibitors of cytochrome P450 (CYP) enzymes. This approach combines liquid chromatography mass spectrometry (LC MS) detection methods with multiple toxicity endpoints to enable identification of critical metabolic pathways for hepatotoxicity. The incubations were performed in the absence and presence of the non-specific CYP inhibitor, 1-aminobenzotriazole (ABT) and isoform-specific inhibitors. The metabolite profile of precocene I in rat liver slices shares some features of the in vivo profile, but also had a major difference in that epoxide dihydrodiol hydrolysis products were not observed to a measurable extent. As examples of our liver slice metabolite identification procedure, a minor glutathione adduct and previously unreported 7-O-desmethyl and glucuronidated metabolites of precocene I are reported. Precocene I induced hepatocellular necrosis in a dose- and time-dependent manner. ABT decreased the toxicity of precocene I, increased exposure to parent compound, and decreased metabolite levels in a dose-dependent manner. Of the isoform-specific CYP inhibitors tested for an effect on the precocene I metabolite profile, only tranylcypromine was noticeably effective, indicating a role of CYPs 2A6, 2C9, 2Cl9, and 2E1. With respect to toxicity, the order of CYP inhibitor effectiveness was ABT > diethyldithiocarbamate∼tranylcypromine > ketoconazole. Furafylline and sulfaphenazole had no effect, while quinidine appeared to augment precocene I toxicity. These results suggest that rat liver slices do not reproduce the reported in vivo biotransformation of precocene I and therefore may not be an appropriate model for precocene I metabolism. However, these results provide an example of how small molecule manipulation of CYP activity in an in vitro model can be used to confirm metabolism-mediated toxicity.  相似文献   
97.
Incubation of the drug-sensitive H69, a small cell lung cancer cell line, with increased concentrations of adriamycin yielded multidrug resistant (MDR) H69AR cells that over-express multidrug resistance-associated protein (MRP1). MRP1 co-transports its substrate with glutathione (GSH), leading to lower intracellular GSH. In this report we tested whether depleting intracellular GSH in MRP1-expressing cells could hyper-sensitize them to anticancer drugs or not. We have found that the GSH contents in MRP1-expressing cells are significantly lower than their corresponding control cells. The treatment with MRP1 substrate verapamil or the GSH synthetase inhibitor buthionine sulfoxi-mine significantly reduced the intracellular GSH contents in MRP1-expressing cells. Interestingly, depleting intracellular GSH contents can hyper-sensitize the MRP1-cDNA transfected BHK cells to daunomycin, but not the adriamycin-selected H69AR cells. Further analyses indicated that anti-apoptotic factor Bcl2 might be a factor responsible for the fact that depleting intracellular GSH could not hyper-sensitize H69AR cells to daunomycin. We hypothesized that knocking down the expression of Bcl2 could hyper-sensitize H69AR cells to daunomycin. Interestingly, infection of H69AR cells with retroviral particles harboring Bcl2 interfering RNAi not only reduced the expression of Bcl2, but also many factors that contribute to MDR, such as Bcl-xl, MRP1 and ABCC3, etc., leading to the MDR H69AR cells more sensitive to daunomycin than the parental H69 cell. Thus, although the mechanisms of the down-regulation of the genes contributing to MDR remain to be elucidated, retroviral particles harboring Bcl2 interfering RNAi could be used as an alternative way to sensitize the MDR cancer cells to anticancer drugs.  相似文献   
98.
脱氧核糖核酸对谷胱甘肽过氧化物酶活性影响的初步研究   总被引:4,自引:0,他引:4  
谷胱甘肽过氧化物酶是机体内重要抗氧酶系之一。它的活力和含量,反映机体清除自由基的能力。自由基对细胞结构的损伤很大,随着年龄的增长,抗氧化酶活力逐渐下降,从而引起自由基及脂质过氧化产物日益增多,最终导致机体衰老和老年性疾病的发生^[1]。本试验试图探讨DNA对谷胱甘肽过氧化物酶活性影响从而探索DNA对抗自由基的作用。  相似文献   
99.
To unveil what controls mitochondrial ROS detoxification, the NADPH supply and GSH/GSSG recycling for oxidative stress management were analyzed in cancer and non-cancer mitochondria. Therefore, proteomic and kinetomic analyses were carried out of the mitochondrial (i) NADPH producing and (ii) GSH/GSSG recycling enzymes associated to oxidative stress management. The protein contents of the eight enzymes analyzed were similar or even higher in AS-30D rat hepatoma mitochondria (HepM) than in rat liver (RLM) and rat heart (RHM) mitochondria, suggesting that the NADPH/GSH/ROS pathway was fully functional in cancer mitochondria.The Vmax values of IDH-2 were much greater than those of GDH, TH and ME, suggesting that IDH-2 is the predominant NADPH producer in the three mitochondrial types; in fact, the GDH reverse reaction was favored. The Vmax values of GR and GPx were lower in HepM than in RLM, suggesting that the oxidative stress management is compromised in cancer mitochondria. The Km values of IDH-2, GR and GPx were all similar among the different mitochondrial types.Kinetic modeling revealed that the oxidative stress management was mainly controlled by GR, GPx and IDH. Modeling and experimentation also revealed that, due to their higher IDH-2 activity and lower GPx activity presumably by acetylation, HepM (i) showed higher steady-state NADPH levels; (ii) required greater peroxide concentrations to achieve reliable steady-state fluxes and metabolite concentration; and (iii) endured higher peroxide concentrations without collapsing their GSH/GSSG ratios. Then, to specifically prompt lower GSH/GSSG ratios under oxidative stress thus compromising cancer mitochondria functioning, GPx should be re-activated.  相似文献   
100.
The ratio of isothiocyanates (ITCs) to nitriles formed in the myrosinase-catalyzed hydrolysis of glucosinolates is a key factor determining the physiological effect of glucosinolate containing plants and materials. In this context, the mechanism by which nitrile formation occurs is not well understood. In the present paper we have studied the effect of three redox reagents – Fe2+, glutathione (GSH) and ascorbic acid – on the profile of products obtained upon the hydrolysis of a model glucosinolate (glucosibarin ((2R)-2-hydroxy-2-phenylethylglucosinolate)) catalyzed by Brassica carinata myrosinase. A Micellar Electrokinetic Capillary Chromatography method that allows following on-line the hydrolysis of the glucosinolate, the formation of the degradation products and the oxidation of GSH was used. Increasing the concentration of Fe2+ and GSH (from 0.25- to 2-fold molar excess with respect to the glucosinolate) increased the ratio of nitrile ((2R)-2-hydroxy-2-phenylethylcyanide) to oxazolidine-2-thione ((5S)-5-phenyloxazolidine-2-thione), whereas increasing the concentration of ascorbic acid decreased this ratio. Low concentrations of ascorbic acid favored nitrile formation. A mechanism for nitrile formation involving a disulfide bond in the myrosinase complex is proposed.  相似文献   
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