PubMed

Metabolomics: A potential way to know the role of vitamin D on multiple sclerosis. J Pharm Biomed Anal. 2016 Dec 29;136:22-31 Authors: Luque-Córdoba D, Luque de Castro MD Abstract The literature about the influence of vitamin D on multiple sclerosis (MS) is very controversial, possibly as a result of the way through which the research on the subject has been conducted. The studies developed so far have been focused exclusively on gene expression: the effect of a given vitamin D metabolite on target receptors. The influence of the vitamin D status (either natural or after supplementation) on MS has been studied by measurement of the 25 monohydroxylated metabolite (also known as circulating form), despite the 1,25 dihydroxylated metabolite is considered the active form. In the light of the multiple metabolic pathways in which both forms of vitamin D (D2 and D3) are involved, monitoring of the metabolites is crucial to know the activity of the target enzymes as a function of both the state of the MS patient and the clinical treatment applied. The study of metabolomics aspects is here proposed to clarify the present controversy. In "omics" terms, our proposal is to take profit from up-stream information-thus is, from metabolomics to genomics-with a potential subsequent step to systems biology, if required. PMID: 28063332 [PubMed - as supplied by publisher]

NMR Metabolomics Investigates the Influence of Flavonoid- Enriched Rations on Chicken Plasma. J AOAC Int. 2017 Jan 07;: Authors: Fotakis C, Lantzouraki DZ, Goliomytis M, Simitzis PE, Charismiadou M, Deligeorgis SG, Zoumpoulakis P Abstract The use of flavonoids as dietary supplements is well established, mainly due to their intense antioxidant and anti-inflammatory properties. In the present study, hesperidin, naringin, and vitamin E were used as additives at different concentrations in poultry rations in order to achieve meat of improved quality. NMR metabolomics was applied to chicken blood serum samples to discern whether and how the enriched rations affected the animals’ metabolic profile. Variations in the metabolic patterns according to sustenance consumption were traced by orthogonal projections to latent structures discriminant analysis (OPLS-DA) models and were attributed to specific metabolites by using S-line plots. In particular, serum samples from chickens fed with vitamin E displayed higher concentrations of glycine and succinic acid compared to control samples, which were mainly characterized by betaine, formic acid, and lipoproteins. Samples from chickens fed with hesperidin were characterized by increased levels of lactic acid, citric acid, creatine, carnosine, creatinine, phosphocreatine, anserine, glucose, and alanine compared to control samples. Lastly, naringin samples exhibited increased levels of citric and acetic acids. Results verify the scalability of NMR metabolomics to highlight metabolite variations among chicken serum samples in relation to food rations. PMID: 28063211 [PubMed - as supplied by publisher]

Related Articles Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome. Environ Int. 2017 Jan 03;: Authors: Andra SS, Austin C, Patel D, Dolios G, Awawda M, Arora M Abstract Global profiling of xenobiotics in human matrices in an untargeted mode is gaining attention for studying the environmental chemical space of the human exposome. Defined as the study of a comprehensive inclusion of environmental influences and associated biological responses, human exposome science is currently evolving out of the metabolomics science. In analogy to the latter, the development and applications of high resolution mass spectrometry (HRMS) has shown potential and promise to greatly expand our ability to capture the broad spectrum of environmental chemicals in exposome studies. HRMS can perform both untargeted and targeted analysis because of its capability of full- and/or tandem-mass spectrum acquisition at high mass accuracy with good sensitivity. The collected data from target, suspect and non-target screening can be used not only for the identification of environmental chemical contaminants in human matrices prospectively but also retrospectively. This review covers recent trends and advances in this field. We focus on advances and applications of HRMS in human biomonitoring studies, and data acquisition and mining. The acquired insights provide stepping stones to improve understanding of the human exposome by applying HRMS, and the challenges and prospects for future research. PMID: 28062070 [PubMed - as supplied by publisher]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/01/07PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Prospective associations of plasma phospholipids and mild cognitive impairment/dementia among African Americans in the ARIC Neurocognitive Study. Alzheimers Dement (Amst). 2017;6:1-10 Authors: Li D, Misialek JR, Boerwinkle E, Gottesman RF, Sharrett AR, Mosley TH, Coresh J, Wruck LM, Knopman DS, Alonso A Abstract INTRODUCTION: The objective of this study was to investigate whether 10 phospholipids/metabolites previously identified as prospectively predictive of mild cognitive impairment (MCI) or dementia in whites would also be predictive in a mostly African-American cohort. METHODS: We repeatedly measured 188 phospholipids/metabolites in plasma samples of 221 participants of the Atherosclerosis Risk in Communities study, 97% African American, who were followed between 2004-2006 and 2011-2013. RESULTS: After a mean follow-up of 7.3 years, 77 were classified as having MCI and 18 as having dementia. Our study failed to replicate previous findings in this mostly African American cohort, in that the 10 phospholipids/metabolites only achieved a C statistic/AUC of 0.609 in predicting development of MCI or dementia (compared to 0.96) and 0.607 in distinguishing normal from MCI or dementia at the follow-up visit. CONCLUSION: A panel of 10 phospholipids/metabolites previously associated with incident dementia was not predictive of MCI or dementia in an independent cohort. PMID: 28054030 [PubMed - in process]

Related Articles Metabolomic analysis identifies differentially produced oral metabolites, including the oncometabolite 2-hydroxyglutarate, in patients with head and neck squamous cell carcinoma. BBA Clin. 2017 Jun;7:8-15 Authors: Mukherjee PK, Funchain P, Retuerto M, Jurevic RJ, Fowler N, Burkey B, Eng C, Ghannoum MA Abstract BACKGROUND: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. METHODS: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS). RESULTS: Among 28 samples obtained from 7 HNSCC cases and 7 controls, 422 metabolites were detected (269 identified and 153 unidentified). Oral washes contained 12 and 23 metabolites in healthy controls and HNSCC patients, respectively, with phosphate and lactate being the most abundant. Small molecules related to energy metabolism were significantly elevated in HNSCC patients compared to controls. Levels of beta-alanine, alpha-hydroxyisovalerate, tryptophan, and hexanoylcarnitine were elevated in HNSCC oral washes compared to healthy controls (range 7.8-12.2-fold). Resection tissues contained 22 metabolites, of which eight were overproduced in tumor by 1.9- to 12-fold compared to controls. TCA cycle analogs 2-hydroxyglutarate (2-HG) and 3-GMP were detected exclusively in tumor tissues. Targeted quantification of 2-HG in a representative HNSCC patient showed increase in tumor tissue (14.7 μg/mL), but undetectable in normal tissue. Moreover, high levels of 2-HG were detected in HNSCC cell lines but not in healthy primary oral keratinocyte cultures. CONCLUSIONS: Oral metabolites related to energy metabolism were elevated in HNSCC, and acylcarnitine and 2HG may have potential as non-invasive biomarkers. Further validation in clinical studies is warranted. PMID: 28053877 [PubMed]

Related Articles Metabolomic and elemental analysis of camel and bovine urine by GC-MS and ICP-MS. Saudi J Biol Sci. 2017 Jan;24(1):23-29 Authors: Ahamad SR, Alhaider AQ, Raish M, Shakeel F Abstract Recent studies from the author's laboratory indicated that camel urine possesses antiplatelet activity and anti-cancer activity which is not present in bovine urine. The objective of this study is to compare the volatile and elemental components of bovine and camel urine using GC-MS and ICP-MS analysis. We are interested to know the component that performs these biological activities. The freeze dried urine was dissolved in dichloromethane and then derivatization process followed by using BSTFA for GC-MS analysis. Thirty different compounds were analyzed by the derivatization process in full scan mode. For ICP-MS analysis twenty eight important elements were analyzed in both bovine and camel urine. The results of GC-MS and ICP-MS analysis showed marked difference in the urinary metabolites. GC-MS evaluation of camel urine finds a lot of products of metabolism like benzene propanoic acid derivatives, fatty acid derivatives, amino acid derivatives, sugars, prostaglandins and canavanine. Several research reports reveal the metabolomics studies on camel urine but none of them completely reported the pharmacology related metabolomics. The present data of GC-MS suggest and support the previous studies and activities related to camel urine. PMID: 28053567 [PubMed - in process]

Related Articles TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1. Blood. 2017 Jan 04;: Authors: Jahn L, Hombrink P, Hagedoorn RS, Kester MG, van der Steen DM, Rodriguez T, Pentcheva-Hoang T, de Ru AH, Schoonakker MP, Meeuwsen MH, Griffioen M, van Veelen PA, Falkenburg JH, Heemskerk MH Abstract Immunotherapy of hematological malignancies or solid tumors by administration of monoclonal antibodies or T-cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hampers the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B-cell specific transcription factor BOB1 presented in the context of HLA-B*07:02. TCR gene transfer installed BOB1-specificity and reactivity onto recipient T-cells. TCR-transduced T-cells efficiently lysed primary B-cell leukemia, mantel cell lymphoma and multiple myeloma in vitro. We also observed recognition and lysis of healthy BOB1-expressing B-cells. In addition, strong BOB1-specific proliferation could be demonstrated for TCR-modified T-cells upon antigen encounter. Furthermore, clear in vivo antitumor reactivity was observed of BOB1-specific TCR-engineered T-cells in a xenograft mouse model of established multiple myeloma. Absence of reactivity towards a broad panel of BOB1-negative but HLA-B*07:02(pos) nonhematopoietic and hematopoietic cells indicated no off-target toxicity. Therefore, administration of BOB1-specific TCR-engineered T-cells may provide novel cellular treatment options to patients suffering from B-cell malignancies including multiple myeloma. PMID: 28053195 [PubMed - as supplied by publisher]

Related Articles Metabolites Associated With Lean Mass and Adiposity in Older Black Men. J Gerontol A Biol Sci Med Sci. 2017 Jan 03;: Authors: Murphy RA, Moore SC, Playdon M, Meirelles O, Newman AB, Milijkovic I, Kritchevsky SB, Schwartz A, Goodpaster BH, Sampson J, Cawthon P, Simonsick EM, Gerszten RE, Clish CB, Harris TB, Health ABC Study Abstract To identify biomarkers of body mass index, body fat, trunk fat, and appendicular lean mass, nontargeted metabolomics was performed in plasma from 319 black men in the Health, Aging and Body Composition study (median age 72 years, median body mass index 26.8 kg/m(2)). Body mass index was calculated from measured height and weight; percent fat, percent trunk fat, and appendicular lean mass were measured with dual-energy x-ray absorptiometry. Pearson partial correlations between body composition measures and metabolites were adjusted for age, study site, and smoking. Out of 350 metabolites, body mass index, percent fat, percent trunk fat, and appendicular lean mass were significantly correlated with 92, 48, 96, and 43 metabolites at p less than .0014. Metabolites most strongly correlated with body composition included carnitine, a marker of fatty acid oxidation (positively correlated), triacylglycerols (positively correlated), and amino acids including branched-chain amino acids (positively correlated except for acetylglycine and serine). Gaussian Graphical Models of metabolites found that 25 lipid metabolites clustered into a single network. Groups of five amino acids, three plasmalogens, and two carnitines were also observed. Findings confirm prior reports of associations between amino acids, lean mass, and fat mass in addition to associations not previously reported. Future studies should consider whether these metabolites are relevant for metabolic disease processes. PMID: 28052980 [PubMed - as supplied by publisher]

Related Articles 2015 ASMS Fall Workshop: Lipids and Lipidomics. J Am Soc Mass Spectrom. 2016 May;27(5):753-6 Authors: Reid GE, Han X PMID: 26975369 [PubMed - indexed for MEDLINE]

Understanding the Molecular Mechanisms of the Interplay Between Herbal Medicines and Gut Microbiota. Med Res Rev. 2017 Jan 04;: Authors: Xu J, Chen HB, Li SL Abstract Herbal medicines (HMs) are much appreciated for their significant contribution to human survival and reproduction by remedial and prophylactic management of diseases. Defining the scientific basis of HMs will substantiate their value and promote their modernization. Ever-increasing evidence suggests that gut microbiota plays a crucial role in HM therapy by complicated interplay with HM components. This interplay includes such activities as: gut microbiota biotransforming HM chemicals into metabolites that harbor different bioavailability and bioactivity/toxicity from their precursors; HM chemicals improving the composition of gut microbiota, consequently ameliorating its dysfunction as well as associated pathological conditions; and gut microbiota mediating the interactions (synergistic and antagonistic) between the multiple chemicals in HMs. More advanced experimental designs are recommended for future study, such as overall chemical characterization of gut microbiota-metabolized HMs, direct microbial analysis of HM-targeted gut microbiota, and precise gut microbiota research model development. The outcomes of such research can further elucidate the interactions between HMs and gut microbiota, thereby opening a new window for defining the scientific basis of HMs and for guiding HM-based drug discovery. PMID: 28052344 [PubMed - as supplied by publisher]

Change of the metabolomic profile during short-term mononuclear cell storage. Vox Sang. 2017 Jan 04;: Authors: Steininger PA, Strasser EF, Ziehe B, Eckstein R, Rauh M Abstract BACKGROUND AND OBJECTIVES: Short-term storage of leukapheresis products used for immunotherapeutic mononuclear cell (MNC) products is a frequent event. The analysis of time-related metabolic patterns enables the characterization of storage-related effects in MNCs and the hypothesis-based optimization of the MNC medium. MATERIALS AND METHODS: The MNC products from seven leukapheresis procedures were stored within a closed bag system for 48 h. Concentrations of amino acids, biogenic amines, phospho- and sphingolipids and hexoses in the medium were measured by targeted metabolomics. The viability of MNC subpopulations was assayed by Annexin V (AnV) and JC-1 staining. RESULTS: Glucose depletion and a significant change of the acylcarnitine profile are early events within the first 24 h of storage. In contrast, for most amino acids, the maximum increase was observed at 48 h of storage as mirrored by an increase in the amino acid levels by a mean factor of 1·2 (1·3, 2·0) after 6 h (24 h, 48 h, respectively). This was except for the concentrations of glutamine and lysine, which did not change significantly. The taurine concentration showed a twofold increase within the first 24 h and remained constant thereafter. The steepest increase in AnV(+) and 7-AAD(+) CD4(+) T cells was found between 24 and 48 h. CONCLUSION: The time-course of apoptosis and metabolic patterns in the MNC products demonstrate that 24 h of storage is a decisive time-point, as afterwards key metabolic pathways showed nonlinear detrimental changes. Optimization of storage by supplementation of specific substrates demands therefore an early intervention. PMID: 28052337 [PubMed - as supplied by publisher]

NEIL3-Dependent Regulation of Cardiac Fibroblast Proliferation Prevents Myocardial Rupture. Cell Rep. 2017 Jan 03;18(1):82-92 Authors: Olsen MB, Hildrestrand GA, Scheffler K, Vinge LE, Alfsnes K, Palibrk V, Wang J, Neurauter CG, Luna L, Johansen J, Øgaard JD, Ohm IK, Slupphaug G, Kuśnierczyk A, Fiane AE, Brorson SH, Zhang L, Gullestad L, Louch WE, Iversen PO, Østlie I, Klungland A, Christensen G, Sjaastad I, Sætrom P, Yndestad A, Aukrust P, Bjørås M, Finsen AV Abstract Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-enriched cell fraction. Neil3(-/-) mice show increased mortality after MI caused by myocardial rupture. Genome-wide analysis of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) reveals changes in the cardiac epigenome, including in genes related to the post-MI transcriptional response. Differentially methylated genes are enriched in pathways related to proliferation and myofibroblast differentiation. Accordingly, Neil3(-/-) ruptured hearts show increased proliferation of fibroblasts and myofibroblasts. We propose that NEIL3-dependent modulation of DNA methylation regulates cardiac fibroblast proliferation and thereby affects extracellular matrix modulation after MI. PMID: 28052262 [PubMed - in process]

Glycosylation Signatures of Inflammation Identify Cardiovascular Risk: Some Glyc It Hot. Circ Res. 2016 Nov 11;119(11):1154-1156 Authors: Lawler PR, Mora S PMID: 28051777 [PubMed - in process]

Metabolic profiling of root exudates from two ecotypes of Sedum alfredii treated with Pb based on GC-MS. Sci Rep. 2017 Jan 04;7:39878 Authors: Luo Q, Wang S, Sun LN, Wang H Abstract Phytoremediation is an effective method to remediate Pb-contaminated soils and root exudates play an important role in this process. Based on gas chromatography-mass spectrometry (GC-MS) and metabolomics method, this study focuses on the comparative metabolic profiling analysis of root exudates from the Pb-accumulating and non-accumulating ecotypes of Sedum alfredii treated with 0 and 50 μmol/L Pb. The results obtained show that plant type and Pb stress can significantly change the concentrations and species of root exudates, and fifteen compounds were identified and assumed to be potential biomarkers. Leaching experiments showed that l-alanine, l-proline and oxalic acid have a good effect to activate Pb in soil, glyceric acid and 2-hydroxyacetic acid have a general effect to activate Pb in soil. 4-Methylphenol and 2-methoxyphenol might be able to activate Pb in soil, glycerol and diethyleneglycol might be able to stabilize Pb in soil, but these activation effect and stabilization effect were all not obvious. PMID: 28051189 [PubMed - in process]

Gelified biofluids for HRMAS (1)H NMR analysis: the case of urine. Anal Chem. 2017 Jan 03;: Authors: Takis PG, Tenori L, Ravera E, Luchinat C Abstract In this letter we propose an alternative, effective protocol for metabolomic characterization of biofluids based on their gelification and subsequent application of high resolution magic angle spinning (HRMAS) (1)H nuclear magnetic resonance (NMR). The sample handling is very rapid and reproducible, and much less than 40 μl of neat urine are needed to obtain a sample. Our results indicate that the HRMAS spectra of gelified urine encompass all metabolites in the NMR fingerprint, as observed by solution NMR. The proposed approach can be efficiently integrated into the NMR based metabolomics analyses routines: multivariate statistical analysis of both solution and HRMAS data produced very similar statistical models, with high classification accuracy. One of the key advantages offered by the gelification approach is the improved short term (up to 24 hours) preservation of non-frozen HRMAS NMR gel urine samples compared to the solution samples, which could lead to an alternative way for transportation or domestic collection of biofluids, without the need of cold-storage and reducing the risks of leakage. PMID: 28050906 [PubMed - as supplied by publisher]

Related Articles Nutrient Supply and Simulated Herbivory Differentially Alter the Metabolite Pools and the Efficacy of the Glucosinolate-Based Defense System in Brassica Species. J Chem Ecol. 2017 Jan 03;: Authors: Almuziny M, Decker C, Wang D, Gerard P, Tharayil N Abstract Environmental stress hinders growth of plants and commonly results in the accumulation of carbon-based defense compounds. However, the dynamics of nitrogen (N)-containing defense compounds are less predictable under environmental stress. The impact of nutrient deficiency on plant defenses that require the metabolic conversion of a less toxic compound to a more potent toxin is even more poorly understood. We evaluated the effects of nitrogen (N) and potassium (K) deficiency and simulated herbivory on the concentration of metabolites including glucosinolates (GSLs), on the conversion of GSLs to more toxic isothiocyanates (ITCs), and on the activity of myrosinase (MYR) in leaves of Brassica juncea and Brassica nigra. Both species contained GSLs, predominantly sinigrin, but also derivatives of glucobrassicin. Compared to the control, N deficiency increased the sinigrin concentration in both species. Methyl jasmonate (MeJA) application increased sinigrin production in B. junceae, whereas in B. nigra MeJA increased sinigrin only under K-deficiency. Compared to the aliphatic-glucosinolates, MeJA application produced a greater compositional change in the profiles of indolic-glucosinolates. In both species the increase in sinigrin content of the tissue was associated with a decrease in its overall nutritive value as assessed by the content of sugars and amino acids. In B. juncea, application of MeJA decreased the conversion of sinigrin to allyl isothiocyanate (AITC) under both N and K deficiency. The potential activity of MYR decreased in both species under N deficiency. The reduced conversion of sinigrin to AITC and the lower activity of MYR suggest that the GSL-ITC defense system might have a limited efficiency in deterring generalist herbivores under environmental stress. PMID: 28050732 [PubMed - as supplied by publisher]

Related Articles CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes. Proc Natl Acad Sci U S A. 2017 Jan 03;: Authors: Kooy-Winkelaar YM, Bouwer D, Janssen GM, Thompson A, Brugman MH, Schmitz F, de Ru AH, van Gils T, Bouma G, van Rood JJ, van Veelen PA, Mearin ML, Mulder CJ, Koning F, van Bergen J Abstract Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin(-)IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin(-)IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin(-)IELs is driven by epithelial cell-derived IL-15. Like CD, RCDII is strongly associated with HLA-DQ2, suggesting the involvement of HLA-DQ2-restricted gluten-specific CD4(+) T cells. We now show that gluten-specific CD4(+) T cells isolated from CD duodenal biopsy specimens produce cytokines able to trigger proliferation of malignant Lin(-)IEL lines as powerfully as IL-15. Furthermore, we identify TNF, IL-2, and IL-21 as CD4(+) T-cell cytokines that synergistically mediate this effect. Like IL-15, these cytokines were found to increase the phosphorylation of STAT5 and Akt and transcription of antiapoptotic mediator bcl-xL Several small-molecule inhibitors targeting the JAK/STAT pathway blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR pathway blocked proliferation induced by IL-15 as well as the CD4(+) T-cell cytokines. Confirming and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation of freshly isolated Lin(-)IELs and CD3(-)CD56(+) IELs (NK-IELs) from RCDII as well as non-RCDII duodenal biopsy specimens. These data provide evidence implicating CD4(+) T-cell cytokines in the pathogenesis of RCDII. More broadly, they suggest that adaptive immune responses can contribute to innate IEL activation during mucosal inflammation. PMID: 28049849 [PubMed - as supplied by publisher]

Related Articles Crosstalk between alternatively spliced UGT1A isoforms and colon cancer cell metabolism. Mol Pharmacol. 2017 Jan 03;: Authors: Audet-Delage Y, Rouleau M, Rouleau M, Roberge J, Miard S, Picard F, Tetu B, Guillemette C Abstract Alternative splicing at the human glucuronosyltransferase 1 gene locus (UGT1) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized that UGT1A_i2s function into a complex protein network connecting other metabolic pathways with influence on cancer cell metabolism. This is based on a pathway enrichment analysis of proteomic data that identified several high-confidence candidate interaction proteins of UGT1A_i2 proteins in human tissues, namely the rate-limiting enzyme of glycolysis pyruvate kinase (PKM), which plays a critical role in cancer cell metabolism and tumor growth. The partnership of UGT1A_i2 and PKM2 was confirmed by co-immunoprecipitation in the HT115 colon cancer cells and was supported by a partial co-localization of these two proteins. In support of a functional role for this partnership, depletion of UGT1A_i2 proteins in HT115 cells enforced the Warburg effect with higher glycolytic rate at the expense of mitochondrial respiration, and led to lactate accumulation. Untargeted metabolomics further revealed a significantly altered cellular content of 58 metabolites including many intermediates derived from the glycolysis and TCA cycle pathways. These metabolic changes were associated with a greater migration potential. The potential relevance of our observations is supported by the down-regulation of UGT1A_i2s mRNA in colon tumors compared to normal tissues. Alternate UGT1A variants may thus be part of the expanding compendium of metabolic pathways involved in cancer biology directly contributing to the oncogenic phenotype of colon cancer cells. Findings uncover new aspects of UGT functions diverging from their transferase activity. PMID: 28049773 [PubMed - as supplied by publisher]

Related Articles Integrated Metabolomics and Proteomics Highlight Altered Nicotinamide- and Polyamine Pathways in Lung Adenocarcinoma. Carcinogenesis. 2017 Jan 03;: Authors: Fahrmann JF, Grapov DD, Wanichthanarak K, DeFelice BC, Salemi MR, Rom WN, Gandara DR, Phinney BS, Fiehn O, Pass H, Miyamoto S Abstract Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer (NSCLC) adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of cancer, but the extent of these changes in early stage lung adenocarcinoma remains largely unknown. In the current study, an integrated metabolomics and proteomics approach was utilized to characterize the biochemical and molecular alterations between malignant and matched control tissue from 27 subjects diagnosed with early stage lung adenocarcinoma. Differential analysis identified 71 metabolites and 1102 proteins that delineated tumor from control tissue. Integrated results indicated four major metabolic changes in early stage adenocarcinoma: (1) increased glycosylation and glutaminolysis; (2) elevated Nrf2 activation; (3) increase in nicotinic and nicotinamide salvaging pathways; and (4) elevated polyamine biosynthesis linked to differential regulation of the SAM/nicotinamide methyl-donor pathway. Genomic data from publicly available databases were included to strengthen proteomic findings. Our findings provide insight into the biochemical and molecular biological reprogramming that may accompanies early stage lung tumorigenesis and highlight potential therapeutic targets. PMID: 28049629 [PubMed - as supplied by publisher]