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1.
Toxoplasma gondii Malate dehydrogenase (TgMDH) plays an important role as part of the energy production cycle. In this investigation, immunological changes and protection efficiency of this protein delivered as a DNA vaccine have been evaluated. Mice were intramuscularly immunized with pTgMDH, followed by challenge with virulent T. gondii RH strain, 2 weeks after the booster immunization. Compared to the control groups, the results showed that pTgMDH has stimulated specific humoral response as demonstrated by significant high titers of total IgG and subclasses IgG1 and IgG2a, beside IgA and IgM, but not IgE. Analysis of cytokine profiles revealed significant increases of IFN‐γ, IL‐4 and IL‐17, while no significant changes were detected in TGF‐β1. In cell‐mediated response, both T lymphocytes subpopulations CD4+ and CD8+ were positively recruited as significant percentages were recorded in response to immunization with TgMDH. Significant long survival rate, 17 days, has been observed in the TgMDH vaccinated group, in contrast with control groups which died within 8–9 days after challenge. These results demonstrated that TgMDH could induce significant immunological responses leading to a considerable level of protection against acute toxoplasmosis infection.  相似文献   
2.
Tumor cells have increased glycolytic activity, and glucose is mainly used to form lactate and alanine, even when high concentrations of oxygen are present (Warburg effect). The purpose of the present study was to investigate glucose metabolism in two xenograft models representing basal-like and luminal-like breast cancer using (13) C high-resolution-magic angle spinning (HR-MAS) MRS and gene expression analysis. Tumor tissue was collected from two groups for each model: untreated mice (n=19) and a group of mice (n=16) that received an injection of [1-(13) C]-glucose 10 or 15 min before harvesting the tissue. (13) C HR-MAS MRS was performed on the tumor samples and differences in the glucose/alanine (Glc/Ala), glucose/lactate (Glc/Lac) and alanine/lactate (Ala/Lac) ratios between the models were studied. The expression of glycolytic genes was studied using tumor tissue from the same models. In the natural abundance MR spectra, a significantly lower Glc/Ala and Glc/Lac ratio (p<0.001) was observed in the luminal-like model compared with the basal-like model. In the labeled samples, the predominant glucose metabolites were lactate and alanine. Significantly lower Glc/Ala and Glc/Lac ratios were observed in the luminal-like model (p<0.05). Most genes contributing to glycolysis were expressed at higher levels in the luminal-like model (fdr<0.001). The lower Glc/Ala and Glc/Lac ratios and higher glycolytic gene expression observed in the luminal-like model indicates that the transformation of glucose to lactate and alanine occurred faster in this model than in the basal-like model, which has a growth rate several times faster than that of the luminal-like model. The results from the present study suggest that the tumor growth rate is not necessarily a determinant of glycolytic activity.  相似文献   
3.

BACKGROUND:

Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type.

METHODS:

A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad‐spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes.

RESULTS:

HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2‐deoxyglucose (2‐DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2‐DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild‐type p53 can partially protect tumor cells from glucose starvation.

CONCLUSIONS:

HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status. Cancer 2011. © 2011 American Cancer Society.  相似文献   
4.
BackgroundThe contribution of liver glycogen catabolism to hyperglycemia and glucose intolerance induced by pharmacological hypercortisolism were investigated.MethodsFor this purpose, adult maleWistar rats that received 1.0 mg/kg dexamethasone (DEX) ip at 8:00 a.m. (DEX group) or saline (CON group) once a day for 5 consecutive days were compared.ResultsExperimental hypercortisolism was confirmed by higher (p < 0.05) glycemia, lower (p < 0.05) body weight and glucose intolerance. In the fed state, the basal glycogen catabolism and the glucagon (1 nM) and epinephrine (2 μM) induced glycogen catabolism were similar between the groups. The activation of glycogen catabolism induced by phenylephrine (2 μM) and isoproterenol (20 μM) were increased (p < 0.05) and decreased (p < 0.05), respectively, in DEX rats. Furthermore, DEX rats exhibited higher (p < 0.05) glycogen catabolism during the infusion of cAMP (3 μM). However, during the infusion of cAMP (15 μM), 6MBcAMP (3 μM) or cyanide (0.5 mM), the intensification of glycogen breakdown was similar. Thus, in general, hypercortisolism does not influence the basal glycogen catabolism and the liver responsiveness to glycogenolytic agents in the fed state. In contrast with fed state, fasted rats (DEX group) showed a more intense (p < 0.05) basal glycogen catabolism.ConclusionThe contribution of glycogen catabolism to hyperglycemia during hypercortisolism depends of the nutritional status, starting from a negligible participation in the fed state up to a significant contribution in the fasted state.  相似文献   
5.
目的:探讨LINC00462 招募转录因子 MYC 激活 ABCC3 对肾透明细胞癌(ccRCC)顺铂敏感性的影响及其机制。方法:数据库分析ccRCC 组织中ABCC3、MYC和LINC00462 的表达及其相关性,并分析ABCC3 基因的富集通路。常规培养人肾小管上皮细胞(HK-2)和ccRCC 细胞(A-498、786-O 和 Caki-2),将 si-LINC00462、oe-ABCC3、si-ABCC3、si-MYC、si-LINC00462-NC、oe-ABCC3-NC、si-ABCC3-NC 和 si-MYC-NC 核酸序列分别转染 A-498 或786-O 细胞,分为si-LINC00462组、si-LINC00462-NC 组、oe-ABCC3 组、oe-ABCC3-NC 组、si-ABCC3 组、si-ABCC3-NC 组、si-MYC 组、si-MYC-NC 组;用2-脱氧-D-葡萄糖(2-DG)进行回复实验,构建oe-NC+PBS 组、oe-ABCC3+PBS组、oe-ABCC3+2-DG组;为探究ccRCC细胞LINC00462/MYC/ABCC3 轴对顺铂敏感性的影响,构建si-NC+oe-NC 组、si-LINC00462+oe-NC 组、si-LINC00462+oe-ABCC3 组。qPCR 法检测ABCC3、MYC和LINC00462 在ccRCC细胞中的表达,CCK-8法检测细胞增殖活力,CCK-8法分析梯度浓度顺铂处理ccRCC细胞后IC50值,WB法检测糖酵解代谢途径相关蛋白的表达,Seahorse XP96 法检测各处理组细胞的胞外酸化率(ECAR)和耗氧率(OCR),试剂盒检测细胞中丙酮酸、乳酸、ATP水平。双荧光素酶报告基因和染色质免疫共沉淀(ChIP)实验验证ABCC3与MYC间的结合关系,RNA结合蛋白免疫沉淀(RIP)实验验证LINC00462 和MYC的结合关系。结果:数据库分析和qPCR实验结果显示,ABCC3在ccRCC组织和细胞中呈高表达,差异基因富集在糖酵解通路上。敲减或过表达ABCC3能够增加A-498细胞或降低786-O细胞对顺铂的敏感性,ABCC3可通过促进有氧糖酵解抑制A-498 细胞对顺铂的敏感性,2-DG处理可以逆转过表达ABCC3对ccRCC 细胞对顺铂敏感性的抑制作用。MYC可直接和ABCC3结合,LINC00462 可招募转录因子MYC;敲低LINC00462 可抑制ABCC3的表达,敲低LINC00462 可抑制ccRCC细胞的有氧糖酵解,并提高其对顺铂敏感性;而进一步过表达ABCC3可逆转敲低LINC00462 对ccRCC 细胞有氧糖酵解的抑制作用和顺铂敏感性的提高。结论:LINC00462 通过招募转录因子MYC 激活ABCC3的表达促进ccRCC细胞的糖酵解,进而促进ccRCC细胞对顺铂敏感性。  相似文献   
6.
目的 研究薯蓣素对人口腔鳞状细胞癌的抑制作用。方法 薯蓣素处理TSCCa 和TCa8113 细胞,MTS 和软琼脂集落实验检测薯蓣素对口腔鳞状细胞癌增殖的影响。蛋白质免疫印迹检测薯蓣素对口腔鳞状细胞癌 糖酵解调控蛋白及凋亡调控分子表达的影响。检测过表达己糖激酶HK2 对薯蓣素诱导细胞凋亡的作用。结果 薯蓣素抑制TSCCa 和TCa8113 细胞的增殖具有剂量和时间依赖性(P <0.05)。薯蓣素抑制口腔鳞状细胞癌 糖酵解(P <0.05),并下调HK2 和葡萄糖转运蛋白Glut1 的表达。薯蓣素能诱导口腔鳞状细胞癌Caspase-3 和 PARP 剪切体表达上调,过表达HK2 抑制薯蓣素诱导的细胞凋亡。结论 薯蓣素对口腔鳞状细胞癌的抑制作用 与其下调HK2 和对糖酵解的抑制有关。  相似文献   
7.

目的  探讨缺氧状态下前列腺癌细胞糖酵解和体外迁移侵袭能力的改变。方法  将前列腺癌细胞DU145和/或PC-3分别置于常氧及缺氧环境中培养24和48 h,侵袭小室实验检测前列腺癌细胞体外迁移及侵袭能力改变。分别检测上清液中葡萄糖含量、乳酸含量;实时定量逆转录-聚合酶链反应(qRT-PCR)检测糖酵解相关基因的表达改变。结果  前列腺癌细胞DU145经缺氧处理后,体外迁移及侵袭能力较常氧处理增强。同时缺氧处理后,DU145和PC-3细胞培养上清液中葡萄糖含量减少,肿瘤细胞摄入葡萄糖能力提高,糖酵解代谢产物乳酸在上清液中增加。qRT-PCR结果表明,缺氧处理后DU145细胞糖酵解相关基因。结论  缺氧处理能增强前列腺癌细胞的体外迁移及侵袭能力,同时通过改变糖酵解相关基因的表达,对前列腺癌细胞的糖酵解过程发挥调控作用。

  相似文献   
8.
9.
A shift in our understanding of macrophage biology has come about as a result of recent discoveries in the area of metabolic reprogramming of macrophages. The NLRP3 inflammasome drives the activation of caspase-1, leading to the production of IL-1β, IL-18, and a type of cell death termed pyroptosis. The NLRP3 inflammasome has been shown to sense metabolites such as palmitate, uric acid, and cholesterol crystals and is inhibited by ketone bodies produced during metabolic flux. The NLRP3 inflammasome has also been shown to be regulated by mitochondrial reactive oxygen species and components of glycolysis, such as Hexokinase. Here, we review these findings and discuss their importance for inflammation and furthermore discuss potential therapeutic benefits of targeting NLRP3.  相似文献   
10.
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