PubMed

Related Articles MALDI-MS Imaging in the Study of Glomerulonephritis. Methods Mol Biol. 2017;1618:85-94 Authors: Smith A, Galli M, L'Imperio V, Pagni F, Magni F Abstract Glomerulonephritis (GNs) are one of the most frequent causes of chronic kidney disease (CKD), a renal condition that often leads to end-stage renal failure, and a careful assessment of these diseases is essential for prognostic and therapeutic purposes. The application of MALDI-MSI directly on bioptic renal tissue represents a new stimulating perspective and facilitates the detection of specific proteomic indicators that are directly correlated with the pathological alterations that occur within the glomeruli during the development of glomerulonephritis. Here, we describe the standard workflow for the MALDI-MSI analysis of clinical fresh-frozen and FFPE renal biopsies and highlight how the obtained molecular information, when combined with histology, can be used to detect specific protein markers of GNs. PMID: 28523502 [PubMed - indexed for MEDLINE]

Related Articles MALDI-MSI Analysis of Cytological Smears: The Study of Thyroid Cancer. Methods Mol Biol. 2017;1618:37-47 Authors: Mosele N, Smith A, Galli M, Pagni F, Magni F Abstract Fine needle aspiration (FNA) biopsies are the current gold-standard for the preoperative evaluation of thyroid nodules. However, a significant number of them (15-30%) are unable to be affirmatively diagnosed and are given an "indeterminate for malignancy" final report, meaning that the malignant nature of the thyroid nodule remains unknown and the recommended therapeutic approach is total thyroidectomy. Furthermore, cytomorphological evaluation of biopsies taken post-surgery indicates that approximately 80% of nodules within this group of patients are in fact benign, and the total thyroidectomy unwarranted. Therefore, the identification of new possible diagnostic targets that can assist in the preoperative diagnosis of thyroid tumors and reduce the number of unnecessary thyroidectomies is imperative.Matrix-Assisted Laser Desorption/Ionization (MALDI)-Mass Spectrometry Imaging (MSI) has the ability to provide very precise and localized information regarding protein expression in cytological specimens. This enables the detection of cell subpopulations based on their different protein profiles, even within regions that are indistinguishable at the microscopic level, and the feasibility of this approach to investigate FNA specimens has already been highlighted in a number of studies. Here, an overview about the sample preparation procedure for the MALDI-MSI analysis of ex vivo FNA biopsies is provided, highlighting how molecular imaging can be combined with traditional histology to generate protein signatures of the different thyroid lesions, and, ultimately, build classification models that can be potentially used to classify benign and malignant thyroid nodules from a molecular standpoint. PMID: 28523498 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling-multitude of technologies with great research potential, but (when) will translation emerge? Int J Epidemiol. 2016 10;45(5):1311-1318 Authors: Ala-Korpela M, Davey Smith G PMID: 27789667 [PubMed - indexed for MEDLINE]

Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis through IL-6/JAK2/STAT3 signaling blockade with strong metabolic regulations. Life Sci. 2018 Feb 24;: Authors: Singh AK, Kumar U, Raj V, Maurya V, Kumar D, Maity B, Prakash A, De A, Samanta A, Saha S Abstract AIMS: In quest for alternative drugs to the well known paullones, recently we synthesized novel paullone-like scaffold, 5H-benzo [2,3][1,4]oxazepino[5,6-b]indoles, where compounds 13a (Ta) and 14a (Tb) attenuated liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. Other objective was to explore the ability of FOIs to regulate metabolic perturbations during hepatocellular carcinoma (HCC). MAIN METHODS: A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR and western blot analyses. Further, 1H NMR based metabolomics study was performed to unveil metabolite discriminations among various studied groups. KEY FINDINGS: FOIs exerted notable antitumor effects as evidenced through restoration of body weight, oxidative stress parameters, liver marker enzymes, histological architecture and decrease in cancerous nodules. We identified that FOIs down-regulated the level of IL-6 that was over-expressed during NDEA-induced HCC. It was further confirmed that FOIs obliterated IL-6 over-expression, with concomitant blockade of JAK2-STAT3 signals. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC and provided evidence of their cellular functioning. In particular, the anticancer efficacy of Ta was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. SIGNIFICANCE: These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer. PMID: 29486150 [PubMed - as supplied by publisher]

Silencing barley cystatins HvCPI-2 and HvCPI-4 specifically modifies leaf responses to drought stress. Plant Cell Environ. 2018 Feb 27;: Authors: Velasco-Arroyo B, Diaz-Mendoza M, Gomez-Sanchez A, Moreno-Garcia B, Santamaria ME, Torija-Bonilla M, Hensel G, Kumlehn J, Martinez M, Diaz I Abstract Protein breakdown and mobilization are some of the major metabolic features associated with abiotic stresses, essential for nutrient recycling and plant survival. Genetic manipulation of protease and/or protease inhibitors may contribute to modulate proteolytic processes and plant responses. The expression analysis of the whole cystatin family, inhibitors of C1A cysteine proteases, after water deprivation in barley leaves highlighted the involvement of Icy2 and Icy4 cystatin genes. Artificial microRNA lines independently silencing the two drought-induced cystatins were generated to assess their function in planta. Phenotype alterations at the final stages of the plant life cycle are represented by the stay-green phenotype of silenced cystatin 2 lines. Besides, the enhanced tolerance to drought and differential responses to water deprivation at the initial growing stages are observed. The mutual compensating expression of Icy2 and Icy4 genes in the silencing lines pointed to their cooperative role. Proteolytic patterns by silencing these cystatins were concomitant with modifications in the expression of potential target proteases, in particular HvPap-1, HvPap-12 and HvPap-16 C1A proteases. Metabolomics analyses lines also revealed specific modifications in the accumulation of several metabolites. These findings support the use of plants with altered proteolytic regulation in crop improvement in the face of climate change. PMID: 29486055 [PubMed - as supplied by publisher]

Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases. Mass Spectrom Rev. 2018 Feb 27;: Authors: Cui L, Lu H, Lee YH Abstract In the past decade, advances in liquid chromatography-mass spectrometry (LC-MS) have revolutionized untargeted metabolomics analyses. By mining metabolomes more deeply, researchers are now primed to uncover key metabolites and their associations with diseases. The employment of untargeted metabolomics has led to new biomarker discoveries and a better mechanistic understanding of diseases with applications in precision medicine. However, many major pertinent challenges remain. First, compound identification has been poor, and left an overwhelming number of unidentified peaks. Second, partial, incomplete metabolomes persist due to factors such as limitations in mass spectrometry data acquisition speeds, wide-range of metabolites concentrations, and cellular/tissue/temporal-specific expression changes that confound our understanding of metabolite perturbations. Third, to contextualize metabolites in pathways and biology is difficult because many metabolites partake in multiple pathways, have yet to be described species specificity, or possess unannotated or more-complex functions that are not easily characterized through metabolomics analyses. From a translational perspective, information related to novel metabolite biomarkers, metabolic pathways, and drug targets might be sparser than they should be. Thankfully, significant progress has been made and novel solutions are emerging, achieved through sustained academic and industrial community efforts in terms of hardware, computational, and experimental approaches. Given the rapidly growing utility of metabolomics, this review will offer new perspectives, increase awareness of the major challenges in LC-MS metabolomics that will significantly benefit the metabolomics community and also the broader the biomedical community metabolomics aspire to serve. PMID: 29486047 [PubMed - as supplied by publisher]

Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation. FASEB J. 2018 Feb 27;:fj201701378RR Authors: Marosi K, Moehl K, Navas-Enamorado I, Mitchell SJ, Zhang Y, Lehrmann E, Aon MA, Cortassa S, Becker KG, Mattson MP Abstract Evolutionary considerations suggest that the body has been optimized to perform at a high level in the food-deprived state when fatty acids and their ketone metabolites are a major fuel source for muscle cells. Because controlled food deprivation in laboratory animals and intermittent energy restriction in humans is a potent physiologic stimulus for ketosis, we designed a study to determine the impact of intermittent food deprivation during endurance training on performance and to elucidate the underlying cellular and molecular mechanisms. Male mice were randomly assigned to either ad libitum feeding or alternate-day food deprivation (ADF) groups, and half of the mice in each diet group were trained daily on a treadmill for 1 mo. A run to exhaustion endurance test performed at the end of the training period revealed superior performance in the mice maintained on ADF during training compared to mice fed ad libitum during training. Maximal O2 consumption was increased similarly by treadmill training in mice on ADF or ad libitum diets, whereas respiratory exchange ratio was reduced in ADF mice on food-deprivation days and during running. Analyses of gene expression in liver and soleus tissues, and metabolomics analysis of blood suggest that the metabolic switch invoked by ADF and potentiated by exercise strongly modulates molecular pathways involved in mitochondrial biogenesis, metabolism, and cellular plasticity. Our findings demonstrate that ADF engages metabolic and cellular signaling pathways that result in increased metabolic efficiency and endurance capacity.-Marosi, K., Moehl, K., Navas-Enamorado, I., Mitchell, S. J., Zhang, Y., Lehrmann, E., Aon, M. A., Cortassa, S., Becker, K. G., Mattson, M. P. Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation. PMID: 29485903 [PubMed - as supplied by publisher]

SWATHtoMRM: Development of High-Coverage Targeted Metabolomics Method Using SWATH Technology for Biomarker Discovery. Anal Chem. 2018 Feb 27;: Authors: Zha H, Cai Y, Yin Y, Wang Z, Li K, Zhu ZJ Abstract The complexity of metabolome presents a great analytical challenge for quantitative metabolite profiling, and restricts the application of metabolomics in biomarker discovery. Targeted metabolomics using multiple-reaction monitoring (MRM) technique has excellent capability for quantitative analysis, but suffers from the limited metabolite coverage. To address this challenge, we developed a new strategy, namely, SWATHtoMRM, which utilizes the broad coverage of SWATH-MS technology to develop high-coverage targeted metabolomics method. Specifically, SWATH-MS technique was first utilized to untargeted profile one pooled biological sample, and to acquire the MS2 spectra for all metabolites. Then, SWATHtoMRM was used to extract the large-scale MRM transitions for targeted analysis with coverage as high as 1000-2000 metabolites. Then, we demonstrated the advantages of SWATHtoMRM method in quantitative analysis such as coverage, reproducibility, sensitivity, and dynamic range. Finally, we applied our SWATHtoMRM approach to discover potential metabolite biomarkers for colorectal cancer (CRC) diagnosis. A high-coverage targeted metabolomics method with 1,303 metabolites in one injection was developed to profile colorectal cancer tissues from CRC patients. 20 potential metabolite biomarkers were discovered and validated for CRC diagnosis. In plasma samples from CRC patients, 17 out of 20 potential biomarkers were further validated to be associated with tumor resection, which may have a great potential in assessing the prognosis of CRC patients after tumor resection. Together, the SWATHtoMRM strategy provides a new way to develop high-coverage targeted metabolomics method, and facilitates the application of targeted metabolomics in disease biomarker discovery. The SWATHtoMRM program is freely available on the Internet (http://www.zhulab.cn/software.php). PMID: 29485856 [PubMed - as supplied by publisher]

Chemometrics comparison of GC-MS and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry Daphnia magna metabolic profiles exposed to salinity. J Sep Sci. 2018 Feb 27;: Authors: Parastar H, Garreta-Lara E, Campos B, Barata C, Lacorte S, Tauler R Abstract The performances of gas chromatography with mass spectrometry and of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry are examined through comparison of Daphnia magna metabolic profiles. Gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with mass spectrometry were used to compare the concentration changes of metabolites under saline conditions. In this regard, a chemometric strategy based on wavelet compression and multivariate curve resolution alternating least squares is used to compare the performances of gas chromatography with mass spectrometry and comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry for the untargeted metabolic profiling of D. magna in control and salinity exposed samples. Examination of the results confirmed the outperformance of comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry over gas chromatography with mass spectrometry for the detection of metabolites in D. magna samples. The peak areas of multivariate curve resolution alternating least squares resolved elution profiles in every sample analyzed by comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry were arranged in a new data matrix that was then modeled by partial least squares discriminant analysis. The control and salt-exposed daphnids samples were discriminated and the most relevant metabolites were estimated using variable importance in projection and selectivity ratio values. Salinity de-regulated 18 metabolites from metabolic pathways involved in protein translation, transmembrane cell transport, carbon metabolism, secondary metabolism, glycolysis, and osmoregulation. This article is protected by copyright. All rights reserved. PMID: 29485703 [PubMed - as supplied by publisher]

An UHPLC-TOF MS metabolomic approach to study the impact of moderate red wine consumption on urinary metabolome. J Proteome Res. 2018 Feb 27;: Authors: Esteban-Fernandez A, Ibañez C, Simó C, Bartolome B, Moreno-Arribas MV Abstract Moderate red wine consumption has been widely described to exert several benefits in human health. This is mainly due to its unique content of bioactive polyphenols, which suffer several modifications along their pass through digestive system, including microbial transformation in the colon and phase II metabolism, to be finally excreted in urine and feces. In order to determine the impact of moderate wine consumption in the overall urinary metabolome of healthy volunteers (n=41), samples from a red wine interventional study (250 mL/day, 28 days) were investigated. Urine (24h) was collected before and after intervention and analyzed by an untargeted UHPLC-TOF MS metabolomics approach. 94 compounds linked to wine consumption, including specific wine components (tartaric acid), microbial-derived phenolic metabolites (5-(dihydroxyphenyl)-γ-valerolactones and 4-hydroxyl-5-(phenyl)-valeric acids) and endogenous compounds were identified. Also, some relationships between parallel fecal and urinary metabolome are discussed. PMID: 29485285 [PubMed - as supplied by publisher]

Related Articles Metabolic changes associated with papillary thyroid carcinoma: A nuclear magnetic resonance-based metabolomics study. Int J Mol Med. 2018 Feb 16;: Authors: Li Y, Chen M, Liu C, Xia Y, Xu B, Hu Y, Chen T, Shen M, Tang W Abstract Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new insights into detailed metabolic changes of PTC, and hold great potential in the treatment of PTC. PMID: 29484373 [PubMed - as supplied by publisher]

Related Articles Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery. Genes Nutr. 2018;13:3 Authors: Praticò G, Gao Q, Scalbert A, Vergères G, Kolehmainen M, Manach C, Brennan L, Pedapati SH, Afman LA, Wishart DS, Vázquez-Fresno R, Lacueva CA, Garcia-Aloy M, Verhagen H, Feskens EJM, Dragsted LO Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health. PMID: 29484030 [PubMed]

Related Articles Antibiotic growth promoters virginiamycin and bacitracin methylene disalicylate alter the chicken intestinal metabolome. Sci Rep. 2018 Feb 26;8(1):3592 Authors: Gadde UD, Oh S, Lillehoj HS, Lillehoj EP Abstract Although dietary antibiotic growth promoters have long been used to increase growth performance in commercial food animal production, the biochemical details associated with these effects remain poorly defined. A metabolomics approach was used to characterize and identify the biochemical compounds present in the intestine of broiler chickens fed a standard, unsupplemented diet or a diet supplemented with the antibiotic growth promoters, virginiamycin or bacitracin methylene disalicylate. Compared with unsupplemented controls, the levels of 218 biochemicals were altered (156 increased, 62 decreased) in chickens given the virginiamycin-supplemented diet, while 119 were altered (96 increased, 23 decreased) with the bacitracin-supplemented diet. When compared between antibiotic-supplemented groups, 79 chemicals were altered (43 increased, 36 decreased) in virginiamycin- vs. bacitracin-supplemented chickens. The changes in the levels of intestinal biochemicals provided a distinctive biochemical signature unique to each antibiotic-supplemented group. These biochemical signatures were characterized by increases in the levels of metabolites of amino acids (e.g. 5-hydroxylysine, 2-aminoadipate, 5-hydroxyindoleaceate, 7-hydroxyindole sulfate), fatty acids (e.g. oleate/vaccenate, eicosapentaenoate, 16-hydroxypalmitate, stearate), nucleosides (e.g. inosine, N6-methyladenosine), and vitamins (e.g. nicotinamide). These results provide the framework for future studies to identify natural chemical compounds to improve poultry growth performance without the use of in-feed antibiotics. PMID: 29483631 [PubMed - in process]

Related Articles Elastic net regularized regression for time-series analysis of plasma metabolome stability under sub-optimal freezing condition. Sci Rep. 2018 Feb 26;8(1):3659 Authors: Gonzales GB, De Saeger S Abstract In this paper, the stability of the plasma metabolome at -20 °C for up to 30 days was evaluated using liquid chromatography-high resolution mass spectrometric metabolomics analysis. To follow the time-series deterioration of the plasma metabolome, the use of an elastic net regularized regression model for the prediction of storage time at -20 °C based on the plasma metabolomic profile, and the selection and ranking of metabolites with high temporal changes was demonstrated using the glmnet package in R. Out of 1229 (positive mode) and 1483 (negative mode) metabolite features, the elastic net model extracted 32 metabolites of interest in both positive and negative modes. L-gamma-glutamyl-L-(iso)leucine (tentative identification) was found to have the highest time-dependent change and significantly increased proportionally to the storage time of plasma at -20 °C (R2 = 0.6378 [positive mode], R2 = 0.7893 [negative mode], p-value < 0.00001). Based on the temporal profiles of the extracted metabolites by the model, results show only minimal deterioration of the plasma metabolome at -20 °C up to 1 month. However, majority of the changes appeared at around 12-15 days of storage. This allows scientists to better plan logistics and storage strategies for samples obtained from low-resource settings, where -80 °C storage is not guaranteed. PMID: 29483546 [PubMed - in process]

Related Articles Lkb1 deficiency confers glutamine dependency in polycystic kidney disease. Nat Commun. 2018 Feb 26;9(1):814 Authors: Flowers EM, Sudderth J, Zacharias L, Mernaugh G, Zent R, DeBerardinis RJ, Carroll TJ Abstract Polycystic kidney disease (PKD) is a common genetic disorder characterized by the growth of fluid-filled cysts in the kidneys. Several studies reported that the serine-threonine kinase Lkb1 is dysregulated in PKD. Here we show that genetic ablation of Lkb1 in the embryonic ureteric bud has no effects on tubule formation, maintenance, or growth. However, co-ablation of Lkb1 and Tsc1, an mTOR repressor, results in an early developing, aggressive form of PKD. We find that both loss of Lkb1 and loss of Pkd1 render cells dependent on glutamine for growth. Metabolomics analysis suggests that Lkb1 mutant kidneys require glutamine for non-essential amino acid and glutathione metabolism. Inhibition of glutamine metabolism in both Lkb1/Tsc1 and Pkd1 mutant mice significantly reduces cyst progression. Thus, we identify a role for Lkb1 in glutamine metabolism within the kidney epithelia and suggest that drugs targeting glutamine metabolism may help reduce cyst number and/or size in PKD. PMID: 29483507 [PubMed - in process]

Related Articles Deletion of the neural tube defect-associated gene Mthfd1l disrupts one-carbon and central energy metabolism in mouse embryos. J Biol Chem. 2018 Feb 26;: Authors: Bryant JD, Sweeney SR, Sentandreu E, Shin M, Ipas H, Xhemalce B, Momb J, Tiziani S, Appling DR Abstract One-carbon (1C) metabolism is a universal folate-dependent pathway essential for de novo purine and thymidylate synthesis, amino acid interconversion, universal methyl-donor production, and regeneration of redox cofactors. Homozygous deletion of the 1C pathway gene Mthfd1l encoding methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like, which catalyzes mitochondrial formate production from 10-formyltetrahydrofolate, results in 100% penetrant embryonic neural tube defects (NTDs), underscoring the central role of mitochondrially derived formate in embryonic development and providing a mechanistic link between folate and NTDs. However, the specific metabolic processes that are perturbed by Mthfd1l deletion are not known. Here, we performed untargeted metabolomics on whole Mthfd1l-null and wild-type mouse embryos in combination with isotope tracer analysis in mouse embryonic fibroblast (MEF) cell lines to identify Mthfd1l deletion-induced disruptions in 1C metabolism, glycolysis, and the TCA cycle. We found that maternal formate supplementation largely corrects these disruptions in Mthfd1l-null embryos. Serine tracer experiments revealed that Mthfd1l-null MEFs have altered methionine synthesis, indicating that Mthfd1l deletion impairs the methyl cycle. Supplementation of Mthfd1l-null MEFs with formate, hypoxanthine, or combined hypoxanthine and thymidine restored their growth to wild-type levels. Thymidine addition alone was ineffective, suggesting a purine synthesis defect in Mthfd1l-null MEFs. Tracer experiments also revealed lower proportions of labeled hypoxanthine and inosine monophosphate in Mthfd1l-null than in wild-type MEFs, suggesting that Mthfd1l deletion results in increased reliance on the purine salvage pathway. These results indicate that disruptions of mitochondrial 1C metabolism have wide-ranging consequences for many metabolic processes, including those that may not directly interact with 1C metabolism. PMID: 29483189 [PubMed - as supplied by publisher]

Related Articles Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes. J Biol Chem. 2018 Feb 26;: Authors: Bruegger JJ, Smith BC, Wynia-Smith SL, Marletta MA Abstract Cysteine S-nitrosation is a reversible posttranslational modification mediated by nitric oxide (·NO)-derived agents. S-nitrosation participates in cellular signaling and is associated with several diseases such as cancer, cardiovascular diseases, and neuronal disorders. Despite the physiological importance of this nonclassical ·NO signaling pathway, little is understood about how much S-nitrosation affects protein function. Moreover, identifying physiologically relevant targets of S-nitrosation is difficult because of the dynamics of transnitrosation and a limited understanding of the physiological mechanisms leading to selective protein S-nitrosation. To identify proteins whose activities are modulated by S-nitrosation, we performed a metabolomics study comparing wild-type and endothelial nitric oxide synthase (eNOS) knockout mice. We integrated our results with those of a previous proteomics study that identified physiologically relevant S-nitrosated cysteines, and we found that the activity of at least 21 metabolic enzymes might be regulated by S-nitrosation. We cloned, expressed, and purified four of these enzymes and observed that S-nitrosation inhibits the metabolic enzymes 6-phosphogluconate dehydrogenase (6PGD), Δ1- pyrroline-5-carboxylate dehydrogenase (ALDH4A1), catechol-O-methyltransferase (COMT), and D-3-phosphoglycerate dehydrogenase (PHGDH). Furthermore, using site-directed mutagenesis, we identified the predominate cysteine residue influencing the observed activity changes in each enzyme.In summary, using an integrated metabolomics approach, we have identified several physiologically relevant S-nitrosation targets, including metabolic enzymes, which are inhibited by this modification, and have found the cysteines modified by S-nitrosation in each enzyme. PMID: 29483187 [PubMed - as supplied by publisher]

Related Articles The nephrologist of tomorrow: towards a kidney-omic future. Pediatr Nephrol. 2017 Mar;32(3):393-404 Authors: Hanna MH, Dalla Gassa A, Mayer G, Zaza G, Brophy PD, Gesualdo L, Pesce F Abstract Omics refers to the collective technologies used to explore the roles and relationships of the various types of molecules that make up the phenotype of an organism. Systems biology is a scientific discipline that endeavours to quantify all of the molecular elements of a biological system. Therefore, it reflects the knowledge acquired by omics in a meaningful manner by providing insights into functional pathways and regulatory networks underlying different diseases. The recent advances in biotechnological platforms and statistical tools to analyse such complex data have enabled scientists to connect the experimentally observed correlations to the underlying biochemical and pathological processes. We discuss in this review the current knowledge of different omics technologies in kidney diseases, specifically in the field of pediatric nephrology, including biomarker discovery, defining as yet unrecognized biologic therapeutic targets and linking omics to relevant standard indices and clinical outcomes. We also provide here a unique perspective on the field, taking advantage of the experience gained by the large-scale European research initiative called "Systems Biology towards Novel Chronic Kidney Disease Diagnosis and Treatment" (SysKid). Based on the integrative framework of Systems biology, SysKid demonstrated how omics are powerful yet complex tools to unravel the consequences of diabetes and hypertension on kidney function. PMID: 26961492 [PubMed - indexed for MEDLINE]

32 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 2018/02/27PubMed comprises more than millions of 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.

Common bean varieties demonstrate differential physiological and metabolic responses to the pathogenic fungus Sclerotinia sclerotiorum. Plant Cell Environ. 2018 Feb 24;: Authors: Robison FM, Turner M, Jahn CE, Schwartz HF, Prenni JE, Brick MA, Heuberger AL Abstract Plant physiology and metabolism are important components of a plant response to microbial pathogens. Physiological resistance of common bean (Phaseolus vulgaris L.) to the fungal pathogen Sclerotinia sclerotiorum has been established, but the mechanisms of resistance are largely unknown. Here, the physiological and metabolic responses of bean varieties that differ in physiological resistance to S. sclerotiorum are investigated. Upon infection, the resistant bean variety A195 had a unique physiological response that included reduced photosynthesis and maintaining a higher leaf surface pH during infection. Leaf metabolomics was performed on healthy tissue adjacent to the necrotic lesion at 16, 24, and 48 hours post inoculation, and 144 metabolites were detected that varied between A195 and Sacramento following infection. The metabolites that varied in leaves included amines/amino acids, organic acids, phytoalexins, and ureides. The metabolic pathways associated with resistance included: amine metabolism, uriede-based nitrogen remobilization, antioxidant production, and bean-specific phytoalexin production. A second experiment was conducted in stems of 13 bean genotypes with varying resistance. Stem resistance was associated with phytoalexin production, but unlike leaf metabolism, lipid changes were associated with susceptibility. Taken together, the data supports a multi-faceted, physio-metabolic response of common bean to S. sclerotiorum that mediates resistance. PMID: 29476531 [PubMed - as supplied by publisher]