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

Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study.

Wed, 08/05/2019 - 13:38
Related Articles Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study. Acta Diabetol. 2019 May 06;: Authors: Shokry E, Marchioro L, Uhl O, Bermúdez MG, García-Santos JA, Segura MT, Campoy C, Koletzko B Abstract AIMS: Offspring of mothers suffering from obesity and/or gestational diabetes mellitus (GDM) were reported to be at risk of higher birth weight (BW), later obesity and diabetes. We hypothesize that infant anthropometry changes related to maternal pathological status are due to dysregulated infant metabolism. METHODS: First, we inspected differences in BMI z-scores (z-BMI) between three infant groups: born to normal weight (NW; n = 49), overweight/obese (OV/OB; n = 40) and GDM mothers (n = 27) at birth and 1 year. Then, we inspected associations between cord blood metabolites and 1-year Δ z-BMI in the three infant groups at birth and 1 year. RESULTS: No statistically significant difference was detected in z-BMI between the study groups at birth; however, GDM was associated with heavier infants at 1 year. Regarding the associations between the metabolites and z-BMI, phospholipids, especially those containing polyunsaturated fatty acids, were the species most impacted by the maternal metabolic status, since numerous phosphatidylcholines-PUFA were positively associated with z-BMI in NW but negatively in OV/OB and GDM groups at birth. Conversely, the sum of lysophosphatidylcholines was only positively associated with z-BMI in NW at birth but of no relation in the other two groups. At 1 year, most of the associations seen at birth were reversed in NW and lost in OV/OB and GDM groups. In the NW group, PC-PUFA were found to be negatively associated with Δ z-BMI at 1 year in addition to some medium-chain acylcarnitines, tricarboxylic acid metabolites, Asp and Asn-to-Asp ratio. In OV/OB and GDM groups, the non-esterified fatty acid (NEFA26:0) and His correlated with Δ z-BMI at 1 year in negative and positive directions, respectively. CONCLUSIONS: GDM was associated with overweight in offspring at 1 year, independent of the BW with lack of evidence on existing correlation of this finding with metabolic alterations detected in cord blood metabolome. Associations were found between cord blood metabolites and infant anthropometry at birth and were influenced by maternal OB and GDM. However, an extension of the findings monitored at birth among the three groups was not detected longitudinally showing a lack of predictive power of cord blood metabolome for later development at least 1 year. PMID: 31062097 [PubMed - as supplied by publisher]

Dynamic changes of metabolomics and expression of candicidin biosynthesis gene cluster caused by the presence of a pleiotropic regulator AdpA in Streptomyces ZYJ-6.

Wed, 08/05/2019 - 13:38
Related Articles Dynamic changes of metabolomics and expression of candicidin biosynthesis gene cluster caused by the presence of a pleiotropic regulator AdpA in Streptomyces ZYJ-6. Bioprocess Biosyst Eng. 2019 May 06;: Authors: Liu X, Sun X, He W, Tian X, Zhuang Y, Chu J Abstract Candicidin is one of the frequent antibiotics for its high antifungal activity, but the productivity is still extremely low. Introduction of adpA into Streptomyces ZYJ-6 could improve candicidin productivity significantly and achieved 9338 μg/mL, which was the highest value ever reported in the literature. Combined analyses of transcriptional levels, metabolic flux and metabolomics indicate that para-aminobenzoic acid and the first step of shikimic acid metabolism were not the bottleneck for the candicidin production in the control. However, methylmalonyl-CoA played a central role in the candicidin production and the gene methB responsible for the biosynthesis of methylmalonyl-CoA might be the candidate gene target for further improving the production of candicidin. PMID: 31062087 [PubMed - as supplied by publisher]

Methionine is a metabolic dependency of tumor-initiating cells.

Wed, 08/05/2019 - 13:38
Related Articles Methionine is a metabolic dependency of tumor-initiating cells. Nat Med. 2019 May 06;: Authors: Wang Z, Yip LY, Lee JHJ, Wu Z, Chew HY, Chong PKW, Teo CC, Ang HY, Peh KLE, Yuan J, Ma S, Choo LSK, Basri N, Jiang X, Yu Q, Hillmer AM, Lim WT, Lim TKH, Takano A, Tan EH, Tan DSW, Ho YS, Lim B, Tam WL Abstract Understanding cellular metabolism holds immense potential for developing new classes of therapeutics that target metabolic pathways in cancer. Metabolic pathways are altered in bulk neoplastic cells in comparison to normal tissues. However, carcinoma cells within tumors are heterogeneous, and tumor-initiating cells (TICs) are important therapeutic targets that have remained metabolically uncharacterized. To understand their metabolic alterations, we performed metabolomics and metabolite tracing analyses, which revealed that TICs have highly elevated methionine cycle activity and transmethylation rates that are driven by MAT2A. High methionine cycle activity causes methionine consumption to far outstrip its regeneration, leading to addiction to exogenous methionine. Pharmacological inhibition of the methionine cycle, even transiently, is sufficient to cripple the tumor-initiating capability of these cells. Methionine cycle flux specifically influences the epigenetic state of cancer cells and drives tumor initiation. Methionine cycle enzymes are also enriched in other tumor types, and MAT2A expression impinges upon the sensitivity of certain cancer cells to therapeutic inhibition. PMID: 31061538 [PubMed - as supplied by publisher]

Rapid liquid chromatography tandem mass spectrometry method for targeted quantitation of human performance metabolites in saliva.

Wed, 08/05/2019 - 13:38
Related Articles Rapid liquid chromatography tandem mass spectrometry method for targeted quantitation of human performance metabolites in saliva. J Chromatogr A. 2019 Apr 30;: Authors: McBride EM, Lawrence RJ, McGee K, Mach PM, Demond PS, Busch MW, Ramsay JW, Hussey EK, Glaros T, Dhummakupt ES Abstract Saliva is increasingly being targeted for metabolic studies due to its non-invasive collection methods. Tracing levels of certain metabolites within biofluids can provide indications for a myriad of physiological conditions. This study was performed on a panel of eight analytes found in saliva that have shown associations with physiological conditions of human performance, such as stress, inflammation, and circadian rhythm. This dual polarity liquid chromatography tandem mass spectrometric (LCMS/MS) method was developed to accommodate a diverse group of analytes including steroids, alkaloids, and neurotransmitters. Samples collected during field exercises from soldiers were compared to those of civilians and baseline levels of each of these compounds was determined in saliva. Although most analytes showed no significant differences between the two populations, relative cortisol levels were higher for soldiers than for civilians. This developed dual polarity LCMS/MS method can be applied to very diverse groups of salivary analytes simultaneously. PMID: 31060786 [PubMed - as supplied by publisher]

Postprandial Hypertriglyceridaemia Revisited In The Era Of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement.

Wed, 08/05/2019 - 13:38
Related Articles Postprandial Hypertriglyceridaemia Revisited In The Era Of Non-Fasting Lipid Profile Testing: A 2019 Expert Panel Statement. Curr Vasc Pharmacol. 2019 May 07;: Authors: Kolovou GD, Watts GF, Mikhailidis DP, Pérez-Martínez P, Mora S, Bilianou H, Panotopoulos G, Katsiki N, Ooi TC, Lopez-Miranda J, Tybjærg-Hansen A, Tentolouris N, Nordestgaard BG Abstract Residual vascular risk exists despite aggressive lowering of low density lipoprotein cholesterol (LDL-C). A contributor to this residual risk may be elevated fasting, or non-fasting, levels of triglyceride (TG)-rich lipoproteins. Therefore, there is a need to establish whether a standardised oral fat tolerance test (OFTT) can improve atherosclerotic cardiovascular (CV) disease (ASCVD) risk prediction in addition to a fasting or non-fasting lipid profile. An expert panel considered the role of postprandial hypertriglyceridaemia (as represented by an OFTT) in predicting ASCVD. The panel updated its 2011 statement by considering new studies and various patient categories. The recommendations are based on expert opinion since no hard endpoint trials have been performed, Table 1. Individuals with fasting TG concentration <1 mmol/L (89 mg/dL) commonly do not have an abnormal response to an OFTT. In contrast, those with fasting TG concentration ≥2 mmol/L (175 mg/dL) or non-fasting ≥2.3 mmol/L (200 mg/dL) will usually have an abnormal response. We recommend considering postprandial hypertriglyceridaemia testing when fasting TG concentrations and non-fasting TG concentrations are 1-2 mmol/L (89-175 mg/dL) and 1.3-2.3 mmol/L (115-200 mg/dL), respectively as an additional investigation for metabolic risk prediction along with other risk factors (obesity, current tobacco abuse, metabolic syndrome, hypertension, and diabetes mellitus). The panel proposes that an abnormal TG response to an OFTT (consisting of 75 g fat, 25 g carbohydrate and 10 g proteins) is >2.5 mmol/L (220 mg/dL). Postprandial hypertriglyceridaemia is an emerging factor that may contribute to residual CV risk. This possibility requires further research. A standardised OFTT will allow comparisons between investigational studies. We acknowledge that the OFTT will be mainly used for research to further clarify the role of TG in relation to CV risk. For routine practice, there is a considerable support for the use of a single non-fasting sample. PMID: 31060488 [PubMed - as supplied by publisher]

Comprehensive Investigation of the Effects of Brewing Conditions in Sample Preparation of Green Tea Infusions.

Wed, 08/05/2019 - 13:38
Related Articles Comprehensive Investigation of the Effects of Brewing Conditions in Sample Preparation of Green Tea Infusions. Molecules. 2019 May 04;24(9): Authors: Jin Y, Zhao J, Kim EM, Kim KH, Kang S, Lee H, Lee J Abstract Chemical and biological investigation of green tea has been generally performed while using different infusions that are prepared without consideration of the effects of sample preparation conditions. In this study, for the first time, the effects of green tea brewing conditions on the antioxidant activity and chemical profiles of metabolome and catechin compounds were examined at 60 °C and 95 °C for a period of 5-300 min. The antioxidant capacities of the tea infusions, which were assessed as per 2,2-diphenyl-1-picryl-hydrazyl hydrate (DPPH) radical scavenging activity, depended more on temperature than time. Metabolomics study that was based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF/MS) revealed that the metabolic profiles, including 33 differential metabolites, were significantly changed by temperature and time, with the effects of time being more evident at 95 °C starting after 30 min. Infusions that were brewed at 95 °C for greater than 30 min yielded distinct profiles in the hierarchical clustering analysis. The quantification of eight catechins by UHPLC-QqQ/MS showed that the total catechin level peaked at 95 °C brewing at 10 min, after which the levels of four epi-forms of catechins decreased and those of four non-epi-forms increased, implying the epimerization of catechins over time. These results suggest that the brewing conditions for sample preparation of green tea should be put into careful consideration in studies where green tea extracts are applied as aqueous infusions. PMID: 31060206 [PubMed - in process]

MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG.

Wed, 08/05/2019 - 13:38
Related Articles MCT2 mediates concentration-dependent inhibition of glutamine metabolism by MOG. Nat Chem Biol. 2018 11;14(11):1032-1042 Authors: Fets L, Driscoll PC, Grimm F, Jain A, Nunes PM, Gounis M, Doglioni G, Papageorgiou G, Ragan TJ, Campos S, Silva Dos Santos M, MacRae JI, O'Reilly N, Wright AJ, Benes CH, Courtney KD, House D, Anastasiou D Abstract α-Ketoglutarate (αKG) is a key node in many important metabolic pathways. The αKG analog N-oxalylglycine (NOG) and its cell-permeable prodrug dimethyloxalylglycine (DMOG) are extensively used to inhibit αKG-dependent dioxygenases. However, whether NOG interference with other αKG-dependent processes contributes to its mode of action remains poorly understood. Here we show that, in aqueous solutions, DMOG is rapidly hydrolyzed, yielding methyloxalylglycine (MOG). MOG elicits cytotoxicity in a manner that depends on its transport by monocarboxylate transporter 2 (MCT2) and is associated with decreased glutamine-derived tricarboxylic acid-cycle flux, suppressed mitochondrial respiration and decreased ATP production. MCT2-facilitated entry of MOG into cells leads to sufficiently high concentrations of NOG to inhibit multiple enzymes in glutamine metabolism, including glutamate dehydrogenase. These findings reveal that MCT2 dictates the mode of action of NOG by determining its intracellular concentration and have important implications for the use of (D)MOG in studying αKG-dependent signaling and metabolism. PMID: 30297875 [PubMed - indexed for MEDLINE]

Dietary Patterns among Asian Indians Living in the United States Have Distinct Metabolomic Profiles That Are Associated with Cardiometabolic Risk.

Wed, 08/05/2019 - 13:38
Related Articles Dietary Patterns among Asian Indians Living in the United States Have Distinct Metabolomic Profiles That Are Associated with Cardiometabolic Risk. J Nutr. 2018 07 01;148(7):1150-1159 Authors: Bhupathiraju SN, Guasch-Ferré M, Gadgil MD, Newgard CB, Bain JR, Muehlbauer MJ, Ilkayeva OR, Scholtens DM, Hu FB, Kanaya AM, Kandula NR Abstract Background: Recent studies, primarily in non-Hispanic whites, suggest that dietary patterns have distinct metabolomic signatures that may influence disease risk. However, evidence in South Asians, a group with unique dietary patterns and a high prevalence of cardiometabolic risk, is lacking. Objective: We investigated the metabolomic profiles associated with 2 distinct dietary patterns among a sample of Asian Indians living in the United States. We also examined the cross-sectional associations between metabolomic profiles and cardiometabolic risk markers. Methods: We used cross-sectional data from 145 Asian Indians, aged 45-79 y, in the Metabolic Syndrome and Atherosclerosis in South Asians Living in America (MASALA) pilot study. Metabolomic profiles were measured from fasting serum samples. Usual diet was assessed by using a validated food-frequency questionnaire. We used principal components analysis to derive dietary and metabolomic patterns. We used adjusted general linear regression models to examine associations between dietary patterns, individual food groups, metabolite patterns, and cardiometabolic risk markers. Results: We observed 2 major principal components or metabolite clusters, the first comprised primarily of medium- to long-chain acylcarnitines (metabolite pattern 1) and the second characterized by branched-chain amino acids, aromatic amino acids, and short-chain acylcarnitines (metabolite pattern 2). A "Western/nonvegetarian" pattern was significantly and positively associated with metabolite pattern 2 (all participants: β ± SE = 0.180 ± 0.090, P = 0.05; participants without type 2 diabetes: β ± SE = 0.323 ± 0.090, P = 0.0005). In all participants, higher scores on metabolite pattern 2 were adversely associated with measures of glycemia (fasting insulin: β ± SE = 2.91 ± 1.29, P = 0.03; 2-h insulin: β ± SE = 22.1 ± 10.3, P = 0.03; homeostasis model assessment of insulin resistance: β ± SE = 0.94 ± 0.42, P = 0.03), total adiponectin (β ± SE = -1.46 ± 0.47, P = 0.002), lipids (total cholesterol: β ± SE = 7.51 ± 3.45, P = 0.03; triglycerides: β ± SE = 14.4 ± 6.67, P = 0.03), and a radiographic measure of hepatic fat (liver-to-spleen attenuation ratio: β ± SE = -0.83 ± 0.42, P = 0.05). Conclusions: Our findings suggest that a "Western/nonvegetarian" dietary pattern is associated with a metabolomic profile that is related to an adverse cardiometabolic profile in Asian Indians. Public health efforts to reduce cardiometabolic disease burden in this high-risk group should focus on consuming a healthy plant-based diet. PMID: 29893901 [PubMed - indexed for MEDLINE]

metabolomics; +22 new citations

Tue, 07/05/2019 - 13:30
22 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 2019/05/07PubMed 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; +39 new citations

Mon, 06/05/2019 - 19:21
39 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 2019/05/06PubMed 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

Fri, 03/05/2019 - 21:40
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 2019/05/03PubMed 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; +19 new citations

Thu, 02/05/2019 - 12:23
19 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 2019/05/02PubMed 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; +19 new citations

Wed, 01/05/2019 - 15:01
19 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 2019/05/01PubMed 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; +23 new citations

Tue, 30/04/2019 - 14:46
23 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 2019/04/30PubMed 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.

Impact of different elicitors on grapevine leaf metabolism monitored by 1H NMR spectroscopy.

Mon, 29/04/2019 - 14:38
Related Articles Impact of different elicitors on grapevine leaf metabolism monitored by 1H NMR spectroscopy. Metabolomics. 2019 Apr 27;15(5):67 Authors: Burdziej A, Da Costa G, Gougeon L, Le Mao I, Bellée A, Corio-Costet MF, Mérillon JM, Richard T, Szakiel A, Cluzet S Abstract INTRODUCTION: Grapevine protection is an important issue in viticulture. To reduce pesticide use, sustainable disease control strategies are proposed, including a promising alternative method based on the elicitor-triggered stimulation of the grapevine natural defense responses. However, detailed investigations are necessary to characterize the impact of such defense induction on the primary metabolism. OBJECTIVES: Our aim was to use a metabolomics approach to assess the impact on grapevine of different elicitors dependent on the salicylic acid (SA) and/or jasmonic acid (JA) pathway. For this purpose, leaves of grapevine foliar cuttings were treated with methyl jasmonate, acibenzolar-S-methyl or phosphonates. METHODS: According to the elicitor, common and discriminating metabolites were elucidated using 1H NMR measurements and principal component analysis. RESULTS: A wide range of compounds including carbohydrates, amino acids, organic acids, phenolics and amines were identified. The score plots obtained by combining PC1 versus PC2 and PC1 versus PC3 allowed a clear separation of samples, so metabolite fingerprinting showed an extensive reprogramming of primary metabolic pathways after elicitation. CONCLUSION: The methods applied were found to be accurate for the rapid determination and differential characterization of plant samples based on their metabolic composition. These investigations can be very useful because the application of plant defense stimulators is gaining greater importance as an alternative strategy to pesticides in the vineyard. PMID: 31030265 [PubMed - in process]

Walnuts change lipoprotein composition suppressing TNFα-stimulated cytokine production by diabetic adipocyte.

Mon, 29/04/2019 - 14:38
Related Articles Walnuts change lipoprotein composition suppressing TNFα-stimulated cytokine production by diabetic adipocyte. J Nutr Biochem. 2019 Mar 28;68:51-58 Authors: Borkowski K, Yim SJ, Holt RR, Hackman RM, Keen CL, Newman JW, Shearer GC Abstract Walnut consumption can provide both vascular and metabolic health benefits, and walnut-induced changes in lipoprotein particle chemical payloads may be responsible for these health benefits. To explore this possibility with a focus on metabolic health, this study investigated the impact of walnut consumption on lipoprotein lipid composition and changes in LDL anti-inflammatory properties, as reported by inflamed adipocyte. Hypercholesterolemic, postmenopausal females were treated with 40 g/day (i.e., 1.6 servings/day; n=15) of walnuts for 4 weeks. Fatty acids and their oxygenated metabolites, i.e., oxylipins, were quantified in isolated lipoproteins. Human primary adipocytes were exposed to LDL and TNFα-stimulated adipokine production was measured. Walnut treatment elevated α-linolenic acid and its epoxides in all lipoproteins and depleted mid-chain alcohols in VLDL and LDL, but not HDL. Walnuts also reduced TNFα-induced diabetic adipocyte production of IL-6 (-48%, P=.0006) and IL-8 (-30%, P=.01), changes inversely correlated with levels of α-linolenic acid-derived epoxides but not α-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein lipid profiles and enhance their ability to inhibit TNFα-dependent pro-inflammatory responses in human diabetic primary adipocytes. Moreover, this study suggests the oxylipins, rather than the parent fatty acids, mediate LDL action of adipocytes. PMID: 31030167 [PubMed - as supplied by publisher]

Study on chemical constituents of herbal formula Er Miao Wan and GC-MS based metabolomics approach to evaluate its therapeutic effects on hyperuricemic rats.

Mon, 29/04/2019 - 14:38
Related Articles Study on chemical constituents of herbal formula Er Miao Wan and GC-MS based metabolomics approach to evaluate its therapeutic effects on hyperuricemic rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Apr 19;1118-1119:101-108 Authors: Huang B, Hu X, Wang J, Li P, Chen J Abstract Hyperuricemia strongly correlates with an increased risk of the development of gout, and cardiovascular and kidney diseases, etc. Er Miao Wan (EMW) is a classical traditional Chinese medicine (TCM) formula extensively used for the treatment of hyperuricemia and gout. However, the global components and action mechanism of the formula are still unknown. Here, the chemical constituents of EMW extract were identified by ultra-high performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). A total of 24 alkaloids, 15 organic acids, 4 terpenoids, 3 lactones, 3 glycosides, 46 volatile constituents and 3 other compounds were tentatively identified from the EMW extract. Additionally, based on the hyperuricemic rat model induced by long-term high-fructose feed, a GC-MS based metabolomics approach was conducted to holistically assess the mechanism of EMW. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were applied for screening differential metabolites. A total of 21 metabolites that markedly changed in hyperuricemic rats were identified. Further univariate analysis showed that 9 differential metabolites among them were profoundly reversed by EMW intervention. Metabolic pathway analysis revealed that the variations of these metabolites were mainly associated with glycerolipid metabolism, amino acid metabolism, primary bile acid metabolism, taurine and hypotaurine metabolism and purine metabolism. It was inferred that EMW possibly induced its anti-hyperuricemic effect through restoring multiple disturbed pathways to the normal state. This study could assist with elucidating the potential mechanisms of EMW. PMID: 31030102 [PubMed - as supplied by publisher]

1,4-Dioxane exposure induces kidney damage in mice by perturbing specific renal metabolic pathways: An integrated omics insight into the underlying mechanisms.

Mon, 29/04/2019 - 14:38
Related Articles 1,4-Dioxane exposure induces kidney damage in mice by perturbing specific renal metabolic pathways: An integrated omics insight into the underlying mechanisms. Chemosphere. 2019 Apr 17;228:149-158 Authors: Qiu J, Cheng J, Xie Y, Jiang L, Shi P, Li X, Swanda RV, Zhou J, Wang Y Abstract 1,4-Dioxane (dioxane), an industrial solvent widely detected in environmental and biological matrices, has potential nephrotoxicity. However, the underlying mechanism by which dioxane induces kidney damage remains unclear. In this study, we used an integrated approach, combining kidney transcriptomics and urine metabolomics, to explore the mechanism for the toxic effects of dioxane on the mouse kidney. Transcriptomics profiling showed that exposure to 0.5 mg/L dioxane induced perturbations of multiple signaling pathways in kidneys, such as MAPK and Wnt, although no changes in oxidative stress indicators or anatomical pathology were observed. Exposure to 500 mg/L dioxane significantly disrupted various metabolic pathways, concomitantly with observed renal tissue damage and stimulated oxidant defense system. Urine metabolomic analysis using NMR indicated that exposure to dioxane gradually altered the metabolic profile of urine. Within the full range of altered metabolites, the metabolic pathway containing glycine, serine and threonine was the most significantly altered pathway at the early stage of exposure (3 weeks) in both 0.5 and 500 mg/L dioxane-treated groups. However, with prolonged exposure (9 and 12 weeks), the level of taurine significantly decreased after treatment of 0.5 mg/L dioxane, while exposure to 500 mg/L dioxane significantly increased glutathione levels in urine and decreased arginine metabolism. Furthermore, integrated omics analysis showed that 500 mg/L dioxane exposure induced arginine deficiency by perturbing several genes involved in renal arginine metabolism. Shortage of arginine coupled with increased oxidative stress could lead to renal dysfunction. These findings offer novel insights into the toxicity of dioxane. PMID: 31029960 [PubMed - as supplied by publisher]

PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines.

Mon, 29/04/2019 - 14:38
Related Articles PFOA and PFOS promote diabetic renal injury in vitro by impairing the metabolisms of amino acids and purines. Sci Total Environ. 2019 Apr 16;676:72-86 Authors: Gong X, Yang C, Hong Y, Chung ACK, Cai Z Abstract BACKGROUND: Environmental pollutants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are common surfactants in various consumer products. Epidemiological studies have demonstrated the association of diabetic kidney diseases with PFOA and PFOS. However, mechanisms of metabolic alterations involved are still unclear. METHODS: Considering their involvement of glomerular hemodynamics, rat mesangial cells (MCs) are used as an in vitro model of diabetic kidney diseases for exposure to PFOS/PFOA under diabetic condition. Non-targeted metabolomics studies based on liquid chromatography-high resolution mass spectrometry were conducted to determine how PFOA/PFOS promoted fibrotic and proinflammatory responses in the MCs under diabetic condition. RESULTS: Exposure of PFOA/PFOS (10 μM) increased oxidative stress and the levels of fibrotic and proinflammatory markers in MCs under diabetic condition. We demonstrated for the first time that PFOA and PFOS altered amino acid biosynthesis, citrate cycle, and purine metabolism in MCs under diabetic condition. Compared with diabetic condition, the exposure of PFOA and PFOS under diabetic condition more significantly altered the levels of 13 intracellular metabolites, including L-tyrosine, L-phenylalanine, L-arginine, L-tryptophan, AMP, ADP, UMP, inosine, and hypoxanthine, which have been reported to be related to kidney injury. In addition, PFOA/PFOS treatment significantly altered the expression levels of key enzymes involved in these metabolisms. Treatment with L-tyrosine, L-phenylalanine, L-arginine, and L-tryptophan reduced the levels of fibrotic and inflammatory markers induced by PFOA/PFOS. CONCLUSION: Our results suggest that under diabetic condition, exposure of PFOA or PFOS aggravated diabetic kidney injury in vitro by impairing metabolisms of amino acids and purines to induce more fibrosis and inflammation in MCs. PMID: 31029902 [PubMed - as supplied by publisher]

Proteomic and metabolomic insights into the functions of the male reproductive system in fishes.

Mon, 29/04/2019 - 14:38
Related Articles Proteomic and metabolomic insights into the functions of the male reproductive system in fishes. Theriogenology. 2019 Apr 15;132:182-200 Authors: Dietrich MA, Nynca J, Ciereszko A Abstract Proteomics and metabolomics are emerging and powerful tools to unravel the complex molecular mechanisms regulating reproduction in male fish. So far, numerous proteins and metabolites have been identified that provide us with valuable information to conduct a comprehensive analysis on seminal plasma and spermatozoa components and their functions. These analyses have allowed a better understanding of the blood-testis barrier functions, the molecular mechanisms underlying spermatogenesis, spermatozoa maturation, motility signaling, and competition as well as the mechanism of cryodamage to sperm structure and functions. To extend, proteins that undergo posttranslational modification, such as phosphorylation and oxidation in response to spermatozoa motility activation and cryopreservation, respectively, have been identified. Proteomic studies resulted in identification of potential proteins that can be used as biomarkers for sperm quality and freezability to enable the control of artificial reproduction, and to improve methods for long-term preservation (cryopreservation) of sperm. The different proteins expressed in the spermatozoa of neomales and normal males can also provide new insights into development of methods for separating X and Y fish sperm, and changes in the protein profiles in haploid and diploid spermatozoa will provide new perspectives to better understand the mechanism of male polyploidy. Overall, the knowledge gained by proteomic and metabolomic studies is important from basic to applied sciences for the development and/or optimisation of techniques in controlled fish reproduction. PMID: 31029849 [PubMed - as supplied by publisher]

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