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| 1 | Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort显示文摘BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile. | Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá | 2019 | World Journal of Gastroenterology2019，25，4： | 4 |
| 2 | Arbuscular mycorrhizal symbiosis decreases strigolactone production in tomato 显示文摘 | López-Ráez J A Charnikhova T Fernández I | 2011 | Journal of Plant Physiology2011，168，7： | 1 |
| 3 | Decontamination and disinfection of water by solar photocatalysis:recent overview and trends显示文摘 | Malato S Fernández-Ibá(n)ez P Maldonado M I | | 0，，： | 1 |
| 4 | Some features of the overoxidation of polypyrrole synthesized on austenitic stainless steel electrodes in aqueous nitrate solutions显示文摘 | FERNáNDEZ I TRUEBA M NúńEZ C A | 2005 | Surf Coat Technol2005，191，1： | 1 |
| 5 | Expression of CD10 and renal cell carcinoma marker in clear cell renal cell carcinoma:analysis on tissue arrays显示文摘 | Ortiz-Rey J A G(o)mez De Maria C Pel(a)ez Boismorand E Fern(a)ndez Costas A Barbosa Barreiro M J Ant(o)n Badiola I | 2006 | Actas Urol Esp2006，30，： | 1 |
| 6 | Photocatalytic disinfection of natural well water contaminated by Fusarium solani using TiO2 slurry in solar CPC photo-reactors显示文摘 | Fernández-Ibá?eez P Sichel C Polo-Lpóez M I | | 0，，1： | 1 |
| 7 | 日粮补充或限制维生素A及其时机对育肥猪视黄醇和α-生育酚的积累和基因表达的影响显示文摘补充维生素是提高猪饲料营养价值的方法。某些维生素如维生素A和维生素E都与肉质有关,已有相关报道其可以作为颉颃剂来使用。因此,养猪生产者和消费者对这些维生素在组织中的含量有强烈的兴趣。为研究日粮补充或停止使用维生素的持续时间和时机对育肥猪组织中维生素A的沉积和a-生育酚的积累和基因表达的影响,选取体重16.3±2.5kg的伊比利亚断奶仔猪80头,对照组饲喂富含维生素A的日粮(维生素A10000U·kg-1),早期限饲组(ER组)从试验开始时(猪重16.3kg)饲喂未添加维生素A的日粮,后期限饲组(LR组)从仔猪平均体重达到35.8kg时开始饲喂未添加维生素A的日粮。体重达到101.4kg时,ER、LR组与对照组相比平均日增重和饲料转化率均较低(P=0.001,P=0.034)。而不论是试验初期(〈35.8kg)、肥育期(101.4~157.9kg)还是整个试验期间(16.3-157.9kg)猪的终重、平均日增重、平均日采食量和饲料转化率差异均无显著影响。组织中视黄醇浓度反映了饲料中维生素A的水平。对照组动物肝脏和脂肪库中视黄醇和视黄醇棕榈酸酯的积累在生长期比育肥期更为显著。维生素A限制组的脂肪视黄醇浓度下降,各组织间表现出不同的转移灵敏度,肝脏视黄醇转移更快。ER组肝脏a-生育酚的增加比LR组更显著(P〈0.0001)。而LR组比ER组在a-生育酚水平和脂肪含量的增加更为显着(P〈0.0001);活体重(LW)101kg时,对照组ADHIC基因表达较ER组更高(P=0.0237);LW101、158kg时,ER组LRAT基因的表达呈剂量依赖性下降(P〈0.0001)。RBP4、ALDHIA1、MTTP和TTP基因的表达没有受到日粮处理影响。生长时间影响基因的表达,ADH1C和RBP4基因的表达主要表现在猪101kg时(P〈0.05)。MTTP和TTP基因相对表达量也受时间影响,并且显示出和维生素A相关的基因表达相反的模式。结果表明,日粮长期或短期消除维生素A具有降低饲料的成本、增加组织a-生育酚的水平的潜力,且不影响屠宰重和饲料转化率。 | Ayuso M óvilo C Fernández A Nu?ez Y Isabel B Daza A López-Bote C J Rey A I | 2015 | 饲料博览2015，0，5： | 0 |
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