PubMed

Related Articles Integrative Analysis of PRKAG2 Cardiomyopathy iPS and Microtissue Models Identifies AMPK as a Regulator of Metabolism, Survival, and Fibrosis. Cell Rep. 2016 Dec 20;17(12):3292-3304 Authors: Hinson JT, Chopra A, Lowe A, Sheng CC, Gupta RM, Kuppusamy R, O'Sullivan J, Rowe G, Wakimoto H, Gorham J, Zhang K, Musunuru K, Gerszten RE, Wu SM, Chen CS, Seidman JG, Seidman CE Abstract AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, and ventricular pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show that activating PRKAG2 mutations increase microtissue twitch force by enhancing myocyte survival. Integrating RNA sequencing with metabolomics, PRKAG2 mutations that activate AMPK remodeled global metabolism by regulating RNA transcripts to favor glycogen storage and oxidative metabolism instead of glycolysis. As in patients with PRKAG2 cardiomyopathy, iPS cell and mouse models are protected from cardiac fibrosis, and we define a crosstalk between AMPK and post-transcriptional regulation of TGFβ isoform signaling that has implications in fibrotic forms of cardiomyopathy. Our results establish critical connections among metabolic sensing, myocyte survival, and TGFβ signaling. PMID: 28009297 [PubMed - in process]

Related Articles Metabonomic analysis of ovarian tumour cyst fluid by proton nuclear magnetic resonance spectroscopy. Oncotarget. 2016 Feb 09;7(6):7216-26 Authors: Kyriakides M, Rama N, Sidhu J, Gabra H, Keun HC, El-Bahrawy M Abstract The majority of ovarian tumours are of the epithelial type, which can be sub classified as benign, borderline or malignant. Epithelial tumours usually have cystic spaces filled with cyst fluid, the metabolic profile of which reflects the metabolic activity of the tumour cells, due to their close proximity. The approach of metabonomics using 1H-NMR spectroscopy was employed to characterize the metabolic profiles of ovarian cyst fluid samples (n = 23) from benign, borderline and malignant ovarian tumours in order to shed more light into ovarian tumour and cancer development. The analysis revealed that citrate was elevated in benign versus malignant tumours, while the amino acid lysine was elevated in malignant versus non-malignant tumours, both at a 5% significance level. Choline and lactate also had progressively increasing levels from benign to borderline to malignant samples. Finally, hypoxanthine was detected exclusively in a sub-cohort of the malignant tumours. This metabonomic study demonstrates that ovarian cyst fluid samples have potential to be used to distinguish between the different types of ovarian epithelial tumours. Furthermore, the respective metabolic profiles contain mechanistic information which could help identify biomarkers and therapeutic targets for ovarian tumours. PMID: 26769844 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/12/23PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/12/22PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles IL-6 Linkage to Exercise-Induced Shifts in Lipid-Related Metabolites: A Metabolomics-Based Analysis. J Proteome Res. 2016 Dec 20; Authors: Nieman DC, Sha W, Pappan KL Abstract Metabolomics profiling and bioinformatics technologies were used to determine the relationship between exercise-induced increases in IL-6 and lipid-related metabolites. Twenty-four male runners (age 36.5±1.8 y) ran on treadmills to exhaustion (2.26±0.01 h, 24.9±1.3 km, 69.7±1.9% VO2max). Vastus lateralis muscle biopsy and blood samples were collected before and immediately after running, and showed a 33.7±4.2% decrease in muscle glycogen, 39.0±8.8-, 2.4±0.3-, and 1.4±0.1-fold increases in plasma IL-6, IL-8, and MCP-1, respectively, and 95.0±18.9% and 158±20.6% increases in cortisol and epinephrine, respectively (all, P<0.001). The metabolomics analysis revealed changes in 209 metabolites, especially long- and medium-chain fatty acids, lipid peroxidation products, acylcarnitines, and ketone bodies. OPLS-DA modeling supported a strong separation in pre- and post-exercise samples (R2Y=0.964, Q2Y=0.902). OPLSR analysis failed to produce a viable model for the relationship between IL-6 and all lipid-related metabolites (R2Y = 0.76, Q2Y = - 0.0748). Multiple structure equation models were evaluated based on IL-6, with the best fit pathway model showing a linkage of exercise time to IL-6, then carnitine, and 13-methylmyristic acid (a marker for adipose tissue lipolysis) and sebacate. These metabolomics-based data indicate that the increase in plasma IL-6 after long endurance running has a minor relationship to increases in lipid-related metabolites. PMID: 27996272 [PubMed - as supplied by publisher]

Related Articles Metabolite Variation in Lean and Obese Streptozotocin (STZ)-Induced Diabetic Rats via (1)H NMR-Based Metabolomics Approach. Appl Biochem Biotechnol. 2016 Dec 19; Authors: Abu Bakar Sajak A, Mediani A, Maulidiani, Ismail A, Abas F Abstract Diabetes mellitus (DM) is considered as a complex metabolic disease because it affects the metabolism of glucose and other metabolites. Although many diabetes studies have been conducted in animal models throughout the years, the pathogenesis of this disease, especially between lean diabetes (ND + STZ) and obese diabetes (OB + STZ), is still not fully understood. In this study, the urine from ND + STZ, OB + STZ, lean/control (ND), and OB + STZ rats were collected and compared by using (1)H NMR metabolomics. The results from multivariate data analysis (MVDA) showed that the diabetic groups (ND + STZ and OB + STZ) have similarities and dissimilarities for a certain level of metabolites. Differences between ND + STZ and OB + STZ were particularly noticeable in the synthesis of ketone bodies, branched-chain amino acid (BCAA), and sensitivity towards the oral T2DM diabetes drug metformin. This finding suggests that the ND + STZ group was more similar to the T1DM model and OB + STZ to the T2DM model. In addition, we also managed to identify several pathways and metabolism aspects shared by obese (OB) and OB + STZ. The results from this study are useful in developing drug target-based research as they can increase understanding regarding the cause and effect of DM. PMID: 27995574 [PubMed - as supplied by publisher]

Related Articles Dataset of urinary metabolites measured by (1)H NMR analysis of normal human urine. Data Brief. 2017 Feb;10:227-229 Authors: Cassiède M, Nair S, Dueck M, Mino J, McKay R, Mercier P, Quémerais B, Lacy P Abstract The data in this article are related to the research entitled, "Assessment of (1)H NMR-based metabolomics analysis for normalization of urinary metals against creatinine" (M. Cassiède, S. Nair, M. Dueck, J. Mino, R. McKay, P. Mercier, B. Quémerais, P. Lacy, 2016) [1]. This article describes the analysis of urinary metabolites in normal, healthy individuals by (1)H NMR-based metabolomics. NMR spectra of urine samples typically contain hundreds of peaks that must be carefully screened for reproducibility and detectability. An important requirement in the screening of appropriate urinary metabolites is to ensure that they are reproducibly detected. In our study, we applied the peak profiles of 151 known urinary metabolites to 10 normal human urine samples and found that 50 metabolites were reproducibly measured between 600 and 700 MHz magnets in the same samples. The data set has been made publicly available to enable critical or extended analysis. PMID: 27995159 [PubMed]

Related Articles Harvest year effects on Apulian EVOOs evaluated by (1)H NMR based metabolomics. PeerJ. 2016;4:e2740 Authors: Girelli CR, Del Coco L, Papadia P, De Pascali SA, Fanizzi FP Abstract Nine hundred extra virgin olive oils (EVOO) were extracted from individual olive trees of four olive cultivars (Coratina, Cima di Mola, Ogliarola, Peranzana), originating from the provinces of Bari and Foggia (Apulia region, Southern Italy) and collected during two consecutive harvesting seasons (2013/14 and 2014/15). Following genetic identification of individual olive trees, a detailed Apulian EVOO NMR database was built using 900 oils samples obtained from 900 cultivar certified single trees. A study on the olive oil lipid profile was carried out by statistical multivariate analysis (Principal Component Analysis, PCA, Partial Least-Squares Discriminant Analysis, PLS-DA, Orthogonal Partial Least-Squares Discriminant Analysis, OPLS-DA). Influence of cultivar and weather conditions, such as the summer rainfall, on the oil metabolic profile have been evaluated. Mahalanobis distances and J2 criterion have been measured to assess the quality of resulting scores clusters for each cultivar in the two harvesting campaigns. The four studied cultivars showed non homogeneous behavior. Notwithstanding the geographical spread and the wide number of samples, Coratina showed a consistent behavior of its metabolic profile in the two considered harvests. Among the other three Peranzana showed the second more consistent behavior, while Cima di Mola and Ogliarola having the biggest change over the two years. PMID: 27994965 [PubMed]

Related Articles A simple multi-scale Gaussian smoothing-based strategy for automatic chromatographic peak extraction. J Chromatogr A. 2016 Jun 24;1452:1-9 Authors: Fu HY, Guo JW, Yu YJ, Li HD, Cui HP, Liu PP, Wang B, Wang S, Lu P Abstract Peak detection is a critical step in chromatographic data analysis. In the present work, we developed a multi-scale Gaussian smoothing-based strategy for accurate peak extraction. The strategy consisted of three stages: background drift correction, peak detection, and peak filtration. Background drift correction was implemented using a moving window strategy. The new peak detection method is a variant of the system used by the well-known MassSpecWavelet, i.e., chromatographic peaks are found at local maximum values under various smoothing window scales. Therefore, peaks can be detected through the ridge lines of maximum values under these window scales, and signals that are monotonously increased/decreased around the peak position could be treated as part of the peak. Instrumental noise was estimated after peak elimination, and a peak filtration strategy was performed to remove peaks with signal-to-noise ratios smaller than 3. The performance of our method was evaluated using two complex datasets. These datasets include essential oil samples for quality control obtained from gas chromatography and tobacco plant samples for metabolic profiling analysis obtained from gas chromatography coupled with mass spectrometry. Results confirmed the reasonability of the developed method. PMID: 27207578 [PubMed - indexed for MEDLINE]

Zinc stress affects ionome and metabolome in tea plants. Plant Physiol Biochem. 2016 Dec 12;111:318-328 Authors: Zhang Y, Wang Y, Ding Z, Wang H, Song L, Jia S, Ma D Abstract The research of physiological responses to Zn stress in plants has been extensively studied. However, the ionomics and metabolomics responses of plants to Zn stress remain largely unknown. In present study, the nutrient elements were identified involved in ion homeostasis and metabolomics changes related to Zn deficiency or excess in tea plants. Nutrient element analysis demonstrated that the concentrations of Zn affected the ion-uptake in roots and the nutrient element transportation to leaves, leading to the different distribution of P, S, Al, Ca, Fe and Cu in the tea leaves or roots. Metabolomics analysis revealed that Zn deficiency or excess differentially influenced the metabolic pathways in the tea leaves. More specifically, Zn deficiency affected the metabolism of carbohydrates, and Zn excess affected flavonoids metabolism. Additionally, the results showed that both Zn deficiency and Zn excess led to reduced nicotinamide levels, which speeded up NAD(+) degradation and thus reduced energy metabolism. Furthermore, element-metabolite correlation analysis illustrated that Zn contents in the tea leaves were positively correlated with organic acids, nitrogenous metabolites and some carbohydrate metabolites, and negatively correlated with the metabolites involved in secondary metabolism and some other carbohydrate metabolites. Meanwhile, metabolite-metabolite correlation analysis demonstrated that organic acids, sugars, amino acids and flavonoids played dominant roles in the regulation of the tea leaf metabolism under Zn stress. Therefore, the conclusion should be drawn that the tea plants responded to Zn stress by coordinating ion-uptake and regulation of metabolism of carbohydrates, nitrogenous metabolites, and flavonoids. PMID: 27992770 [PubMed - as supplied by publisher]

Comprehensive metabolomic and lipidomic profiling of human kidney tissue: a platform comparison. J Proteome Res. 2016 Dec 19; Authors: Leuthold P, Schaeffeler E, Winter S, Büttner F, Hofmann U, Mürdter TE, Rausch S, Sonntag D, Wahrheit J, Fend F, Hennenlotter J, Bedke J, Schwab M, Haag M Abstract Metabolite profiling of tissue samples is a promising approach for the characterization of cancer pathways and tumor classification based on metabolic features. Here, we present an analytical method for non-targeted metabolomics of kidney tissue. Capitalizing on different chemical properties of metabolites allowed us to extract a broad range of molecules covering small polar molecules and less polar lipid classes that were analyzed by LC-QTOF-MS after HILIC and RP chromatographic separation, respectively. More than 1000 features could be reproducibly extracted and analyzed (CV < 30%) in porcine and human kidney tissue which were used as surrogate matrices for method development. To further assess assay performance, cross-validation of the non-targeted metabolomics platform to a targeted metabolomics approach was carried out. Strikingly, from 102 metabolites that could be detected on both platforms the majority (>90%) revealed Spearman's correlation coefficients ≥ 0.3, indicating that quantitative results from the non-targeted assay are largely comparable to data derived from classical targeted assays. Finally, as proof-of-concept, the method was applied to human kidney tissue where a clear differentiation between kidney cancer and non-tumorous material could be demonstrated based on unsupervised statistical analysis. PMID: 27992229 [PubMed - as supplied by publisher]

A non-targeted UHPLC-HRMS metabolomics pipeline for metabolite identification; application to cardiac remote ischemic preconditioning. Anal Chem. 2016 Dec 19; Authors: Kouassi Nzoughet J, Bocca C, Simard G, Prunier-Mirebeau D, Chao de la Barca JM, Bonneau D, Procaccio V, Prunier F, Lenaers G, Reynier P Abstract In recent years, the amount of investigations based on non-targeted metabolomics has increased, although often without thorough assessment of analytical strategies applied to acquire data. Following published guidelines for metabolomics experiments, we report a validated non-targeted metabolomics strategy with pipeline for unequivocal metabolites identification using the MSMLS™ molecule library. We achieved an in-house database containing accurate m/z values, retention times, isotopic patterns, full MS and MS/MS spectra. A UHPLC-HRMS Q-Exactive™ method was developed and experimental variations were determined within and between 3 experimental days. The extraction efficiency as well as the accuracy, precision, repeatability, and linearity of the method were assessed, the method demonstrating good performances. The methodology was further blindly applied to plasma from Remote Ischemic Pre-Conditioning (RIPC) rats. Samples, previously analyzed by targeted metabolomics using completely different protocol, analytical strategy and platform, were submitted to our analytical pipeline. A combination of multivariate and univariate statistical analyses was employed. Selection of putative biomarkers from OPLS-DA model and S-plot was combined to jack-knife confidence intervals, metabolites VIP values and univariate statistics. Only variables with strong model contribution and highly statistical reliability were selected as discriminated metabolites. Three biomarkers identified by the previous targeted metabolomics study were found in the current work, in addition to three novel metabolites, emphasizing the efficiency of the current methodology and its ability to identify new biomarkers of clinical interest, in a single sequence. The biomarkers were identified to level 1 according to the Metabolomics Standard Initiative and confirmed by both RPLC and HILIC-HRMS. PMID: 27992159 [PubMed - as supplied by publisher]

Comfortably numb and back: Plasma metabolomics reveals biochemical adaptations in the hibernating thirteen-lined ground squirrel. J Proteome Res. 2016 Dec 19; Authors: D'Alessandro A, Nemkov T, Bogren LK, Martin SL, Hansen KC Abstract Hibernation is an evolutionary adaptation affording some mammals the ability to exploit the cold to achieve extreme metabolic depression (torpor) whilst avoiding ischemia/reperfusion or hemorrhagic shock injuries. Hibernators cycle periodically out of torpor, restoring high metabolic activity. If understood at the molecular level, the adaptations underlying torpor-arousal cycles may be leveraged for translational applications in critical fields such as intensive care medicine. Here, we monitored 266 metabolites to investigate the metabolic adaptations to hibernation in plasma from thirteen-lined ground squirrels (57 animals, 9 timepoints). Results indicate that the periodic arousals foster the removal of potentially toxic oxidative stress-related metabolites which accumulate in plasma during torpor while replenishing reservoirs of circulating catabolic substrates (free fatty acids and amino acids). Specifically, we identified metabolic fluctuations of basic amino acids lysine and arginine, one-carbon metabolism intermediates and sulfur-containing metabolites methionine, cysteine and cystathionine. Conversely, reperfusion injury markers such as succinate/fumarate remained relatively stable across cycles. Considering the cycles of these metabolites with the hibernator's cycling metabolic activity together with their well-established role as substrates for the production of hydrogen sulfide (H2S), we hypothesize that these metabolic fluctuations function as a biological clock regulating torpor to arousal transitions and resistance to reperfusion during arousal. PMID: 27991798 [PubMed - as supplied by publisher]

Anti-melanoma activity of Forsythiae Fructus aqueous extract in mice involves regulation of glycerophospholipid metabolisms by UPLC/Q-TOF MS-based metabolomics study. Sci Rep. 2016 Dec 19;6:39415 Authors: Bao J, Liu F, Zhang C, Wang K, Jia X, Wang X, Chen M, Li P, Su H, Wang Y, Wan JB, He C Abstract Metabolomics is a comprehensive assessment of endogenous metabolites of a biological system in a holistic context. In this study, we evaluated the in vivo anti-melanoma activity of aqueous extract of Forsythiae Fructus (FAE) and globally explored the serum metabolome characteristics of B16-F10 melanoma-bearing mice. UPLC/Q-TOF MS combined with pattern recognition approaches were employed to examine the comprehensive metabolic signatures and differentiating metabolites. The results demonstrated that FAE exhibited remarkable antitumor activity against B16-F10 melanoma in C57BL/6 mice and restored the disturbed metabolic profile by tumor insult. We identified 17 metabolites which were correlated with the antitumor effect of FAE. Most of these metabolites are involved in glycerophospholipid metabolisms. Notably, several lysophosphatidylcholines (LysoPCs) significantly decreased in tumor model group, while FAE treatment restored the changes of these phospholipids to about normal condition. Moreover, we found that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and autotaxin (ATX) were highly expressed in melanoma, and FAE markedly down-regulated their expression. These findings indicated that modulation of glycerophospholipid metabolisms may play a pivotal role in the growth of melanoma and the antitumor activity of FAE. Besides, our results suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma and other malignant tumors. PMID: 27991567 [PubMed - in process]

Distinct urine metabolome after Asian ginseng and American ginseng intervention based on GC-MS metabolomics approach. Sci Rep. 2016 Dec 19;6:39045 Authors: Yang L, Yu QT, Ge YZ, Zhang WS, Fan Y, Ma CW, Liu Q, Qi LW Abstract Ginseng occupies a prominent position in the list of best-selling natural products worldwide. Asian ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) show different properties and medicinal applications in pharmacology, even though the main active constituents of them are both thought to be ginsenosides. Metabolomics is a promising method to profile entire endogenous metabolites and monitor their fluctuations related to exogenous stimulus. Herein, an untargeted metabolomics approach was applied to study the overall urine metabolic differences between Asian ginseng and American ginseng in mice. Metabolomics analyses were performed using gas chromatography-mass spectrometry (GC-MS) together with multivariate statistical data analysis. A total of 21 metabolites related to D-glutamine and D-glutamate metabolism, glutathione metabolism, TCA cycle and glyoxylate and dicarboxylate metabolism, differed significantly under the Asian ginseng treatment; 34 metabolites mainly associated with glyoxylate and dicarboxylate metabolism, TCA cycle and taurine and hypotaurine metabolism, were significantly altered after American ginseng treatment. Urinary metabolomics reveal that Asian ginseng and American ginseng can benefit organism physiological and biological functions via regulating multiple metabolic pathways. The important pathways identified from Asian ginseng and American ginseng can also help to explore new therapeutic effects or action targets so as to broad application of these two ginsengs. PMID: 27991533 [PubMed - in process]

Related Articles Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast. Sci Rep. 2016 Feb 19;6:20856 Authors: Sun X, Hirai G, Ueki M, Hirota H, Wang Q, Hongo Y, Nakamura T, Hitora Y, Takahashi H, Sodeoka M, Osada H, Hamamoto M, Yoshida M, Yashiroda Y Abstract Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4(+) and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z)-octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast. PMID: 26892493 [PubMed - indexed for MEDLINE]

Related Articles Purity matters: A workflow for the valid high-resolution lipid profiling of mitochondria from cell culture samples. Sci Rep. 2016 Feb 19;6:21107 Authors: Kappler L, Li J, Häring HU, Weigert C, Lehmann R, Xu G, Hoene M Abstract Subcellular lipidomics is a novel field of research that requires the careful combination of several pre-analytical and analytical steps. To define a reliable strategy for mitochondrial lipid profiling, we performed a systematic comparison of different mitochondria isolation procedures by western blot analyses and comprehensive high-resolution lipidomics. Using liver-derived HepG2 cells, we compared three common mitochondria isolation methods, differential centrifugation (DC), ultracentrifugation (UC) and a magnetic bead-assisted method (MACS). In total, 397 lipid species, including 32 cardiolipins, could be quantified in only 100 μg (by protein) of purified mitochondria. Mitochondria isolated by UC showed the highest enrichment in the mitochondria-specific cardiolipins as well as their precursors, phosphatidylglycerols. Mitochondrial fractions obtained by the commonly used DC and the more recent MACS method contained substantial contaminations by other organelles. Employing these isolation methods when performing lipidomics analyses from cell culture mitochondria may lead to inaccurate results. To conclude, we present a protocol how to obtain reliable mitochondria-specific lipid profiles from cell culture samples and show that quality controls are indispensable when performing mitochondria lipidomics. PMID: 26892142 [PubMed - indexed for MEDLINE]

Related Articles Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions. Sci Rep. 2016 Feb 16;6:21184 Authors: Lin SH, Liu T, Ming X, Tang Z, Fu L, Schmitt-Kopplin P, Kanawati B, Guan XY, Cai Z Abstract Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell-surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133. PMID: 26878908 [PubMed - indexed for MEDLINE]

Related Articles Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer. Sci Rep. 2016 Feb 15;6:20790 Authors: Tian Y, Xu T, Huang J, Zhang L, Xu S, Xiong B, Wang Y, Tang H Abstract Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high-resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors. PMID: 26876567 [PubMed - indexed for MEDLINE]

Related Articles Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease. Trends Biochem Sci. 2016 Mar;41(3):245-60 Authors: Modjtahedi N, Tokatlidis K, Dessen P, Kroemer G Abstract Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein family that carry (CX9C) type motifs are imported into the mitochondrion with the help of the disulfide relay-dependent MIA import pathway. These evolutionarily conserved proteins are emerging as new cellular factors that control mitochondrial respiration, redox regulation, lipid homeostasis, and membrane ultrastructure and dynamics. We discuss recent insights on the activity of known (CX9C) motif-carrying proteins in mammals and review current data implicating the Mia40/CHCHD4 import machinery in the regulation of their mitochondrial import. Recent findings and the identification of disease-associated mutations in specific (CX9C) motif-carrying proteins have highlighted members of this family of proteins as potential therapeutic targets in a variety of human disorders. PMID: 26782138 [PubMed - indexed for MEDLINE]