Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 min 16 sec ago

Decelerating ageing and biological clocks by autophagy.

Thu, 06/06/2019 - 14:52
Related Articles Decelerating ageing and biological clocks by autophagy. Nat Rev Mol Cell Biol. 2019 Jun 04;: Authors: Lopez-Otín C, Kroemer G PMID: 31164727 [PubMed - as supplied by publisher]

MYC-driven small cell lung cancer is metabolically distinct and vulnerable to arginine depletion.

Thu, 06/06/2019 - 14:52
Related Articles MYC-driven small cell lung cancer is metabolically distinct and vulnerable to arginine depletion. Clin Cancer Res. 2019 Jun 04;: Authors: Chalishazar MD, Wait SJ, Huang F, Ireland AS, Mukhopadhyay A, Lee Y, Schuman S, Guthrie MR, Berrett K, Vahrenkamp J, Hu Z, Kudla M, Modzelewska K, Wang G, Ingolia NT, Gertz J, Lum DH, Cosulich SC, Bomalaski JS, DeBerardinis RJ, Oliver TG Abstract PURPOSE: Small cell lung cancer (SCLC) has been treated clinically as a homogeneous disease, but recent discoveries suggest that SCLC is heterogeneous. Whether metabolic differences exist among SCLC subtypes is largely unexplored. In this study, we aimed to determine whether metabolic vulnerabilities exist between SCLC subtypes that can be therapeutically exploited. EXPERIMENTAL DESIGN: We performed steady state metabolomics on tumors isolated from distinct GEMMs representing the MYC and MYCL-driven subtypes of SCLC. Using genetic and pharmacological approaches, we validated our findings in chemo-naive and resistant human SCLC cell lines, multiple GEMMs, four human cell line xenografts, and four newly-derived PDX models. RESULTS: We discover that SCLC subtypes driven by different MYC family members have distinct metabolic profiles. MYC-driven SCLC preferentially depends on arginine-regulated pathways including polyamine biosynthesis and mTOR pathway activation. Chemo-resistant SCLC cells exhibit increased MYC expression and similar metabolic liabilities as chemo-naive MYC-driven cells. Arginine depletion with pegylated arginine deiminase (ADI-PEG 20) dramatically suppresses tumor growth and promotes survival of mice specifically with MYC-driven tumors, including in GEMMs, human cell line xenografts, and a PDX from a relapsed patient. Finally, ADI-PEG 20 is significantly more effective than the standard of care chemotherapy. CONCLUSIONS: These data identify metabolic heterogeneity within SCLC and suggest arginine deprivation as a subtype-specific therapeutic vulnerability for MYC-driven SCLC. PMID: 31164374 [PubMed - as supplied by publisher]

Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort.

Thu, 06/06/2019 - 14:52
Related Articles Plasma metabolomic signatures associated with long-term breast cancer risk in the SU.VI.MAX prospective cohort. Cancer Epidemiol Biomarkers Prev. 2019 Jun 04;: Authors: Lécuyer L, Dalle C, Lyan B, Demidem A, Rossary A, Vasson MP, Petera M, Lagree M, Ferreira T, Centeno D, Galan P, Hercberg S, Deschasaux M, Partula V, Srour B, Latino-Martel P, Kesse-Guyot E, Druesne-Pecollo N, Durand S, Pujos-Guillot E, Touvier M Abstract BACKGROUND: Breast cancer is a major cause of death in occidental women. The role of metabolism in breast cancer etiology remains unclear. Metabolomics may help to elucidate novel biological pathways and identify new biomarkers in order to predict breast cancer long before symptoms appear. The aim of this study was to investigate whether untargeted metabolomic signatures from blood draws of healthy women could contribute to better understand and predict the long-term risk of developing breast cancer. METHODS: A nested case-control study was conducted within the SU.VI.MAX prospective cohort (13 years of follow-up) to analyze baseline plasma samples of 211 incident breast cancer cases and 211 matched controls by LC-MS mass spectrometry. Multivariable conditional logistic regression models were computed. RESULTS: 3565 ions were detected and 1221 were retained for statistical analysis. 73 ions were associated with breast cancer risk (p<0.01, FDR≤0.2). Notably, we observed that a lower plasma level of O-succinyl-homoserine (0.70[0.55-0.89]) and higher plasma levels of valine/norvaline (1.45[1.15-1.83]), glutamine/isoglutamine (1.33[1.07-1.66]), 5-aminovaleric acid (1.46[1.14-1.87]), phenylalanine (1.43[1.14-1.78]), tryptophan (1.40[1.10-1.79]), γ-glutamyl-threonine (1.39[1.09-1.77]), ATBC (1.41[1.10-1.79]) and pregnene-triol sulfate (1.38[1.08-1.77]) were associated with an increased risk of developing breast cancer during follow-up. CONCLUSIONS: Several pre-diagnostic plasmatic metabolites were associated with long-term breast cancer risk and suggested a role of microbiota metabolism and environmental exposure. IMPACT: After confirmation in other independent cohort studies, these results could help to identify healthy women at higher risk of developing breast cancer in the subsequent decade and to propose a better understanding of the complex mechanisms involved in its etiology. PMID: 31164347 [PubMed - as supplied by publisher]

Omics Studies Revealed the Factors Involved in the Formation of Colony Boundary in Myxococcus xanthus.

Thu, 06/06/2019 - 14:52
Related Articles Omics Studies Revealed the Factors Involved in the Formation of Colony Boundary in Myxococcus xanthus. Cells. 2019 Jun 03;8(6): Authors: Anwar MN, Li ZF, Gong Y, Singh RP, Li YZ Abstract Two unrecognizable strains of the same bacterial species form a distinct colony boundary. During growth as colonies, Myxococcus xanthus uses multiple factors to establish cooperation between recognized strains and prevent interactions with unrecognized strains of the same species. Here, ΔMXAN_0049 is a mutant strain deficient in immunity for the paired nuclease gene, MXAN_0050, that has a function in the colony-merger incompatibility of Myxococcus xanthus DK1622. With the aim to investigate the factors involved in boundary formation, a proteome and metabolome study was employed. Visualization of the boundary between DK1622 and ΔMXAN_0049 was done scanning electron microscope (SEM), which displayed the presence of many damaged cells in the boundary. Proteome analysis of the DK1622- boundary disclosed many possible proteins, such as cold shock proteins, cell shape-determining protein MreC, along with a few pathways, such as RNA degradation, phenylalanine, tyrosine and tryptophan biosynthesis, and Type VI secretion system (T6SS), which may play major roles in the boundary formation. Metabolomics studies revealed various secondary metabolites that were significantly produced during boundary formation. Overall, the results concluded that multiple factors participated in the boundary formation in M. xanthus, leading to cellular damage that is helpful in solving the mystery of the boundary formation mechanism. PMID: 31163575 [PubMed]

A review on remediation of cyanide containing industrial wastes using biological systems with special reference to enzymatic degradation.

Thu, 06/06/2019 - 14:52
Related Articles A review on remediation of cyanide containing industrial wastes using biological systems with special reference to enzymatic degradation. World J Microbiol Biotechnol. 2019 Apr 22;35(5):70 Authors: Sharma M, Akhter Y, Chatterjee S Abstract Cyanide is a nitrile which is used extensively in many industries like jewelry, mining, electroplating, plastics, dyes, paints, pharmaceuticals, food processing, and coal coking. Cyanides pose a serious health hazard due to their high affinity towards metals and cause malfunction of cellular respiration by inhibition of cytochrome c oxidase. This inhibition ultimately leads to histotoxic hypoxia, increased acidosis, reduced the functioning of the central nervous system and myocardial activity. Different physicochemical processes including oxidation by hydrogen peroxide, alkaline chlorination, and ozonization have been used to reduce cyanide waste from the environment. Microbial cyanide degradation which is considered as one the most successful techniques is used to take place through different biochemical/metabolic pathways involving reductive, oxidative, hydrolytic or substitution/transfer reactions. Groups of enzymes involved in microbial degradation are cyanidase, cyanide hydratase, formamidase, nitrilase, nitrile hydratase, cyanide dioxygenase, cyanide monooxygenase, cyanase and nitrogenase. In the future, more advancement of omics technologies and protein engineering will help us to recoup the environment from cyanide effluent. In this review, we have discussed the origin and environmental distribution of cyanide waste along with different bioremediation pathways and enzymes involved therein. PMID: 31011828 [PubMed - indexed for MEDLINE]

Cultural and Metabolomic Studies of a New Phtalides Producer, Lignomyces vetlinianus (Agaricomycetes).

Thu, 06/06/2019 - 14:52
Related Articles Cultural and Metabolomic Studies of a New Phtalides Producer, Lignomyces vetlinianus (Agaricomycetes). Int J Med Mushrooms. 2018;20(11):1031-1045 Authors: Sazanova KV, Psurtseva NV, Shavarda AL Abstract Culture characteristics and metabolomic profiling (on the basis of gas chromatography-mass spectrometry) of 3 strains of Lignomyces vetlinianus were studied. Growth rate, macromorphology, and micromorphology of mycelia grown on various media are described. More than 60 compounds were detected in the mycelial extracts, including amino acids, organic acids that are active during the tricarboxylic acid cycle, sugars, fatty acids, sugar alcohols, and sugar acids. Principal component analysis of low-molecular-weight compounds in mycelial methanol extracts of L. vetlinianus strains at different stages of growth demonstrated that the pattern of mycelial metabolomes grouped by age of the culture indicates a significant relation between the development of the culture and the specificity of its metabolite spectrum. Slow-growing cultures develop gradually and are characterized by several changes in metabolite states. The pattern of points is grouped more tightly for fast-growing strains. The production of crystal-like aggregates was observed for aging mycelia at the stationary phase of growth. These aggregates were isolated from mycelia and identified as clusters of 4,6-dimethoxy-phthalide. The molecular structure of this substance was confirmed by nuclear magnetic resonance analysis. The results show that the concentration of 4,6-dimethoxy-phthalide increased during cultivation. Fruiting bodies contained very small amounts of 4,6-dimethoxy-phthalide compared with amounts in mycelia. It can be assumed that L. vetlinianus is a powerful natural producer of phthalides of biotech-nological interest and can be used as a model to study phenolic metabolism in fungi. PMID: 30806228 [PubMed - indexed for MEDLINE]

metabolomics; +20 new citations

Wed, 05/06/2019 - 14:40
20 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 2019/06/05PubMed 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.

metabolomics; +27 new citations

Tue, 04/06/2019 - 14:30
27 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 2019/06/04PubMed 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.

CDK9 Inhibition Induces a Metabolic Switch that Renders Prostate Cancer Cells Dependent on Fatty Acid Oxidation.

Mon, 03/06/2019 - 17:19
Related Articles CDK9 Inhibition Induces a Metabolic Switch that Renders Prostate Cancer Cells Dependent on Fatty Acid Oxidation. Neoplasia. 2019 May 28;21(7):713-720 Authors: Itkonen HM, Poulose N, Walker S, Mills IG Abstract Cyclin-dependent kinase 9 (CDK9), a key regulator of RNA-polymeraseII, is a candidate drug target for cancers driven by transcriptional deregulation. Here we report a multi-omics-profiling of prostate cancer cell responses to CDK9 inhibition to identify synthetic lethal interactions. These interactions were validated using live-cell imaging, mitochondrial flux-, viability- and cell death activation assays. We show that CDK9 inhibition induces acute metabolic stress in prostate cancer cells. This is manifested by a drastic down-regulation of mitochondrial oxidative phosphorylation, ATP depletion and induction of a rapid and sustained phosphorylation of AMP-activated protein kinase (AMPK), the key sensor of cellular energy homeostasis. We used metabolomics to demonstrate that inhibition of CDK9 leads to accumulation of acyl-carnitines, metabolic intermediates in fatty acid oxidation (FAO). Acyl-carnitines are produced by carnitine palmitoyltransferase enzymes 1 and 2 (CPT), and we used both genetic and pharmacological tools to show that inhibition of CPT-activity is synthetically lethal with CDK9 inhibition. To our knowledge this is the first report to show that CDK9 inhibition dramatically alters cancer cell metabolism. PMID: 31151054 [PubMed - as supplied by publisher]

The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children.

Mon, 03/06/2019 - 17:19
Related Articles The concomitant lower concentrations of vitamins B6, B9 and B12 may cause methylation deficiency in autistic children. J Nutr Biochem. 2019 Apr 24;70:38-46 Authors: Belardo A, Gevi F, Zolla L Abstract Autism spectrum disorder (ASD) is characterized by severe and persistent difficulties in social communication and social interaction at multiple levels. Recently, metabolic disorders have been associated with most cases of patients with ASD. The aim of this study was to investigate, through a new and more sophisticated mass technique, such as UHPLC-mass spectrometry (Q-exactive analyzer), alteration in metabolisms analyzing ASD children urine samples from children showing simultaneous vitamin B6, B9 and B12 deficiencies. This in order to study how these concurrent deficiencies may influence some phenotypic aspects of autistic disorder. Thus, urinary metabolic patterns specific to ASD were explored at an early age in 60 children with ASD, showing lower three vitamins levels, and 60 corresponding controls (age group 3-8, M: F=42:18). The results showed significant block of cystathionine formation with consequent accumulation of homocysteine. A lower glutathione levels (GSH), with reduction of essential intracellular reducing environment required for normal immune function, detoxification capacity and redox-sensitive enzyme activity. Increased concentration of 5-methyltetrahydrofolate, which leads to a lower availability of methyl group and significant decrease in urinary methionine and S-adenosyl-L-methionine (SAM) concentrations, the major methyl donor. The latter justify the well-known reduction in protein and DNA methylation reported in autistic children. As a final consideration, the concomitant deficiencies of all three B vitamins, recorded in a significant number of autistic children, suggests that intestinal dysbiosis in these patients may be the main cause of a reduction in their absorption, in addition to the genetic mutation of a specific gene. PMID: 31151052 [PubMed - as supplied by publisher]

Metabolic adaptation to feed restriction on the green sturgeon (Acipenser medirostris) fingerlings.

Mon, 03/06/2019 - 17:19
Related Articles Metabolic adaptation to feed restriction on the green sturgeon (Acipenser medirostris) fingerlings. Sci Total Environ. 2019 May 11;684:78-88 Authors: Lin CY, Huang LH, Deng DF, Lee SH, Liang HJ, Hung SSO Abstract Food restriction may cause severe biological effects on wildlife and lead to population decline and extinction. The objective of the current study was to examine the metabolic effects on green sturgeon in response to feed restriction. Green sturgeon fingerlings were fed for two weeks at 12.5, 25, 50 and 100% of the optimum feeding rate (OFR), which corresponded to 0.25, 0.50, 1.00, and 2.00% body weight per day. We characterized the changes in hydrophilic and hydrophobic metabolites from extracts of muscle, liver, and kidney using nuclear magnetic resonance spectroscopy followed by multivariate statistical analysis. The results of principal component analysis (PCA) score plots from the analyses of hydrophilic metabolites showed that they exhibited a greater response to feed restriction than hydrophobic metabolites. In general, the hydrophilic metabolites in tissues from fish fed ≦25% of the OFR were separated from those fed 100% of the OFR in the PCA score plots. Among the three types of tissues examined, the overall metabolite changes showed a greater response to feed restriction in kidney tissue than in liver or muscle tissues. Numerous glucogenic amino acids in muscle and most amino acids in the kidney were decreased under feed restriction conditions. A significant decrease in ketone bodies (3-hydroxyisobutyrate) was observed in the muscle. Most fatty acids except for glycerol, phospholipid and cholesterol in the liver and kidney tissues were decreased under feed restriction conditions. Creatine phosphate, taurine and glycine were also significantly increased in tissues under feed restriction conditions. In conclusion, this study suggests that the manipulation of feed restriction under the current conditions perturbed metabolites related to energy metabolism, osmolality regulation, and antioxidation capacity in the sturgeon. PMID: 31150878 [PubMed - as supplied by publisher]

Hazard assessment of Maerua subcordata (Gilg) DeWolf. For selected endpoints using a battery of in vitro tests.

Mon, 03/06/2019 - 17:19
Related Articles Hazard assessment of Maerua subcordata (Gilg) DeWolf. For selected endpoints using a battery of in vitro tests. J Ethnopharmacol. 2019 May 28;:111978 Authors: Gebrelibanos Hiben M, Kamelia L, de Haan L, Spenkelink B, Wesseling S, Vervoort J, Rietjens IMCM Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Maerua subcordata (Gilg) DeWolf is a medicinal and wild food plant growing mainly in east Africa. Especially its root tuber is widely used in traditional medicine to treat several infectious and chronic diseases but also in some toxicity implications like use as abortifacient. AIM OF THE STUDY: the present study applied in silico and in vitro tests to identify possible hazards of M. subcordata (fruit, leaf, root, seed) methanol extracts focusing on developmental toxicity. MATERIALS AND METHODS: Ames test, estrogen receptor alpha (ERα) assay, aryl hydrocarbon receptor (AhR) assay, embryonic stem cell test (EST), and zebrafish embryotoxicity test (ZET) were employed. Besides, a Derek Nexus toxicity prediction was performed on candidate structures obtained from metabolomics profiling of the extracts using liquid chromatography coupled to multistage mass spectroscopy (LC/MSn) and a MAGMa software based structural annotation. RESULTS: Glucosinolates, which degrade to isothiocyanates, and biogenic amines were among the candidate molecules identified in the extracts by LC/MSn - MAGMa software structural annotation. Isothiocyanates and some other candidate molecules suggested a positive mutagenicity alert in Derek toxicity predictions. All the extracts showed negative mutagenicity in the Ames test. However, the Derek predictions also identified endocrine and developmental toxicity as possible endpoints of concern. This was further assessed using in vitro tests. Results obtained reveal that leaf extract shows AhR and ERα agonist activities, inhibited differentiation of ES-D3 stem cells into contracting cardiomyocytes in the EST (p < 0.001) as well as inhibited hatching (p < 0.01) and showed acute toxicity (p < 0.01) in the ZET. Also, the fruit extract showed toxicity (p < 0.05) towards zebrafish embryos and both fruit and seed extracts showed AhR agonist activities while root extract was devoid of activity in all in vitro assays. CONCLUSION: The leaf extract tests positive in in vitro tests that this may point towards a developmental toxicity hazard. The current evaluations did not raise concerns of genotoxicity or developmental toxicity for the fruit, seed and root extracts. This is important given the use of especially these parts of M. subcordata, in traditional medicine and/or as (famine) food. PMID: 31150796 [PubMed - as supplied by publisher]

Defining the Independence of the Liver Circadian Clock.

Mon, 03/06/2019 - 17:19
Related Articles Defining the Independence of the Liver Circadian Clock. Cell. 2019 May 30;177(6):1448-1462.e14 Authors: Koronowski KB, Kinouchi K, Welz PS, Smith JG, Zinna VM, Shi J, Samad M, Chen S, Magnan CN, Kinchen JM, Li W, Baldi P, Benitah SA, Sassone-Corsi P Abstract Mammals rely on a network of circadian clocks to control daily systemic metabolism and physiology. The central pacemaker in the suprachiasmatic nucleus (SCN) is considered hierarchically dominant over peripheral clocks, whose degree of independence, or tissue-level autonomy, has never been ascertained in vivo. Using arrhythmic Bmal1-null mice, we generated animals with reconstituted circadian expression of BMAL1 exclusively in the liver (Liver-RE). High-throughput transcriptomics and metabolomics show that the liver has independent circadian functions specific for metabolic processes such as the NAD+ salvage pathway and glycogen turnover. However, although BMAL1 occupies chromatin at most genomic targets in Liver-RE mice, circadian expression is restricted to ∼10% of normally rhythmic transcripts. Finally, rhythmic clock gene expression is lost in Liver-RE mice under constant darkness. Hence, full circadian function in the liver depends on signals emanating from other clocks, and light contributes to tissue-autonomous clock function. PMID: 31150621 [PubMed - in process]

Untargeted metabolomic profiling of urine from healthy dogs and dogs with chronic hepatic disease.

Mon, 03/06/2019 - 17:19
Related Articles Untargeted metabolomic profiling of urine from healthy dogs and dogs with chronic hepatic disease. PLoS One. 2019;14(5):e0217797 Authors: Lawrence YA, Guard BC, Steiner JM, Suchodolski JS, Lidbury JA Abstract Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography-quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility. PMID: 31150490 [PubMed - in process]

An automatic UPLC-HRMS data analysis platform for plant metabolomics.

Mon, 03/06/2019 - 17:19
Related Articles An automatic UPLC-HRMS data analysis platform for plant metabolomics. Plant Biotechnol J. 2019 May 31;: Authors: Liu P, Zhou H, Zheng Q, Lu P, Yu YJ, Cao P, Chen W, Chen Q Abstract Here we want to introduce our new automatic data analysis platform for untargeted metabolomic analysis of complex plant samples. Many laboratories across the world have adopted ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) as they seek to thoroughly characterize metabolites in complex plant samples, with the larger aim of identifying compounds with impactful biological functions. This article is protected by copyright. All rights reserved. PMID: 31150147 [PubMed - as supplied by publisher]

12-Hydroxy-jasmonoyl-L-isoleucine is an active jasmonate that signals through CORONATINE INSENSITIVE 1 and contributes to the wound response in Arabidopsis.

Mon, 03/06/2019 - 17:19
Related Articles 12-Hydroxy-jasmonoyl-L-isoleucine is an active jasmonate that signals through CORONATINE INSENSITIVE 1 and contributes to the wound response in Arabidopsis. Plant Cell Physiol. 2019 May 31;: Authors: Poudel AN, Holtsclaw RE, Kimberlin A, Sen S, Zeng S, Joshi T, Lei Z, Sumner LW, Singh K, Matsuura H, Koo AJ Abstract 12-hydroxy-jasmonoyl-isoleucine (12OH-JA-Ile) is a metabolite in the catabolic pathway of the plant hormone jasmonate, and is synthesized by the cytochrome P450 subclade 94 enzymes. Contrary to the well-established function of jasmonoyl-isoleucine (JA-Ile) as the endogenous bioactive form of jasmonate, the function of 12OH-JA-Ile is unclear. Here, the potential role of 12OH-JA-Ile in jasmonate signaling and wound response was investigated. Exogenous application of 12OH-JA-Ile mimicked several JA-Ile effects including marker gene expression, anthocyanin accumulation and trichome induction in Arabidopsis thaliana. Genome-wide transcriptomics and untargeted metabolite analyses showed large overlaps between those affected by 12OH-JA-Ile and JA-Ile. 12OH-JA-Ile signaling was blocked by mutation in CORONATINE INSENSITIVE 1. Increased anthocyanin accumulation by 12OH-JA-Ile was additionally observed in tomato and sorghum, and was disrupted by the COI1 defect in tomato jai1 mutant. In silico ligand docking predicted that 12OH-JA-Ile can maintain many of the key interactions with COI1-JAZ1 residues identified earlier by crystal structure studies using JA-Ile as ligand. Genetic alternation of jasmonate metabolic pathways in Arabidopsis to deplete both JA-Ile and 12OH-JA-Ile displayed enhanced jasmonate deficient wound phenotypes and was more susceptible to insect herbivory than that depleted in only JA-Ile. Conversely, mutants overaccumulating 12OH-JA-Ile showed intensified wound responses compared to wild-type with similar JA-Ile content. These data are indicative of 12OH-JA-Ile functioning as an active jasmonate signal and contributing to wound and defense response in higher plants. PMID: 31150089 [PubMed - as supplied by publisher]

metabolomics; +31 new citations

Fri, 31/05/2019 - 19:48
31 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 2019/05/31PubMed 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.

metabolomics; +20 new citations

Thu, 30/05/2019 - 16:35
20 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 2019/05/30PubMed 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.

metabolomics; +20 new citations

Thu, 30/05/2019 - 13:32
20 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 2019/05/30PubMed 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.

GC-MS Method for Metabolic Profiling of Mouse Femoral Head Articular Cartilage Reveals Distinct Effects of Tissue Culture and Development.

Wed, 29/05/2019 - 13:19
Related Articles GC-MS Method for Metabolic Profiling of Mouse Femoral Head Articular Cartilage Reveals Distinct Effects of Tissue Culture and Development. Osteoarthritis Cartilage. 2019 May 25;: Authors: Batushansky A, Lopes EBP, Zhu S, Humphries KM, Griffin TM Abstract OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum. We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between 5 to 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted 6 out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development. PMID: 31136803 [PubMed - as supplied by publisher]

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