PubMed

Related Articles Adult stem cell deficits drive Slc29a3 disorders in mice. Nat Commun. 2019 Jul 03;10(1):2943 Authors: Nair S, Strohecker AM, Persaud AK, Bissa B, Muruganandan S, McElroy C, Pathak R, Williams M, Raj R, Kaddoumi A, Sparreboom A, Beedle AM, Govindarajan R Abstract Mutations exclusively in equilibrative nucleoside transporter 3 (ENT3), the only intracellular nucleoside transporter within the solute carrier 29 (SLC29) gene family, cause an expanding spectrum of human genetic disorders (e.g., H syndrome, PHID syndrome, and SHML/RDD syndrome). Here, we identify adult stem cell deficits that drive ENT3-related abnormalities in mice. ENT3 deficiency alters hematopoietic and mesenchymal stem cell fates; the former leads to stem cell exhaustion, and the latter leads to breaches of mesodermal tissue integrity. The molecular pathogenesis stems from the loss of lysosomal adenosine transport, which impedes autophagy-regulated stem cell differentiation programs via misregulation of the AMPK-mTOR-ULK axis. Furthermore, mass spectrometry-based metabolomics and bioenergetics studies identify defects in fatty acid utilization, and alterations in mitochondrial bioenergetics can additionally propel stem cell deficits. Genetic, pharmacologic and stem cell interventions ameliorate ENT3-disease pathologies and extend the lifespan of ENT3-deficient mice. These findings delineate a primary pathogenic basis for the development of ENT3 spectrum disorders and offer critical mechanistic insights into treating human ENT3-related disorders. PMID: 31270333 [PubMed - in process]

Related Articles Hyaluronan synthase 2 (HAS2) overexpression diminishes the procatabolic activity of chondrocytes by a mechanism independent of extracellular hyaluronan. J Biol Chem. 2019 Jul 03;: Authors: Ishizuka S, Tsuchiya S, Ohashi Y, Terabe K, Askew EB, Ishizuka N, Knudson CB, Knudson W Abstract Osteoarthritis (OA) is a progressive degenerative disease of the joints caused in part by a change in the phenotype of resident chondrocytes within affected joints. This altered phenotype, often termed proinflammatory or procatabolic, features enhanced production of endoproteinases and matrix metallo-proteinases (MMPs) as well as secretion of endogenous inflammatory mediators. Degradation and reduced retention of the proteoglycan aggrecan is an early event in OA. Enhanced turnover of hyaluronan (HA) is closely associated with changes in aggrecan. Here, to determine whether experimentally increased HA production promotes aggrecan retention and generates a positive feedback response, we overexpressed HA synthase-2 (HAS2) in chondrocytes via an inducible adenovirus construct (HAS2-OE). HAS2-OE incrementally increased high-molecular-mass HA > 100-fold within the cell-associated and growth medium pools. More importantly, our results indicated that the HAS2-OE expression system inhibits MMP3, MMP13 and other markers of the procatabolic phenotype (such as TNF-stimulated gene 6 protein [TSG6]) and also enhances aggrecan retention. These markers were inhibited in OA-associated chondrocytes and in chondrocytes activated by interleukin-1β (IL-1β), but also chondrocytes activated by lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), or HA oligosaccharides.  However, the enhanced extracellular HA resulting from HAS2-OE did not reduce the pro-catabolic phenotype of neighboring non-transduced chondrocytes as we had expected.    Rather, HA-mediated inhibition of the phenotype occurred only in transduced cells.  In addition, high HA biosynthesis rates, especially in transduced pro-catabolic chondrocytes, resulted in marked changes in chondrocyte dependence on glycolysis versus oxidative phosphorylation for their metabolic energy needs. PMID: 31270213 [PubMed - as supplied by publisher]

Related Articles Steroyl-CoA Desaturase 1 (SCD1) protects ovarian cancer cells from ferroptotic cell death. Cancer Res. 2019 Jul 03;: Authors: Tesfay L, Paul BT, Konstorum A, Deng Z, Cox AO, Lee J, Furdui CM, Hegde P, Torti FM, Torti SV Abstract Activation of ferroptosis, a recently described mechanism of regulated cell death, dramatically inhibits growth of ovarian cancer cells. Given the importance of lipid metabolism in ferroptosis and the key role of lipids in ovarian cancer, we examined the contribution to ferroptosis of steroyl CoA desaturase (SCD1), an enzyme that catalyzes the rate-limiting step in monounsaturated fatty acid synthesis, in ovarian cancer cells. SCD1 was highly expressed in ovarian cancer tissue, cell lines, and a genetic model of ovarian cancer stem cells. Inhibition of SCD1 induced lipid oxidation and cell death. Conversely, over-expression of SCD1 or exogenous administration of its C16:1 and C18:1 products, palmitoleicic acid or oleate, protected cells from death. Inhibition of SCD1 induced both ferroptosis and apoptosis: inhibition of SCD1 decreased CoQ10, an endogenous membrane antioxidant whose depletion has been linked to ferroptosis, while concomitantly decreasing unsaturated fatty acyl chains in membrane phospholipids and increasing long chain saturated ceramides, changes previously linked to apoptosis. Simultaneous triggering of two death pathways suggests SCD1 inhibition may be an effective component of anti-tumor therapy, since overcoming this dual mechanism of cell death may present a significant barrier to the emergence of drug resistance. Supporting this concept, we observed that inhibition of SCD1 significantly potentiated the anti-tumor effect of ferroptosis inducers in both ovarian cancer cell lines and a mouse orthotopic xenograft model. Our results suggest that the use of combined treatment with SCD1 inhibitors and ferroptosis inducers may provide a new therapeutic strategy for patients with ovarian cancer. PMID: 31270077 [PubMed - as supplied by publisher]

Related Articles Chitosan Oligosaccharide Ameliorates Nonalcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Mice. Mar Drugs. 2019 Jul 02;17(7): Authors: Qian M, Lyu Q, Liu Y, Hu H, Wang S, Pan C, Duan X, Gao Y, Qi LW, Liu W, Wang L Abstract Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially triglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD. PMID: 31269758 [PubMed - in process]

Related Articles A Single Visualization Technique for Displaying Multiple Metabolite-Phenotype Associations. Metabolites. 2019 Jul 02;9(7): Authors: Henglin M, Niiranen T, Watrous JD, Lagerborg KA, Antonelli J, Claggett BL, Demosthenes EJ, von Jeinsen B, Demler O, Vasan RS, Larson MG, Jain M, Cheng S Abstract To assist with management and interpretation of human metabolomics data, which are rapidly increasing in quantity and complexity, we need better visualization tools. Using a dataset of several hundred metabolite measures profiled in a cohort of ~1500 individuals sampled from a population-based community study, we performed association analyses with eight demographic and clinical traits and outcomes. We compared frequently used existing graphical approaches with a novel 'rain plot' approach to display the results of these analyses. The 'rain plot' combines features of a raindrop plot and a conventional heatmap to convey results of multiple association analyses. A rain plot can simultaneously indicate effect size, directionality, and statistical significance of associations between metabolites and several traits. This approach enables visual comparison features of all metabolites examined with a given trait. The rain plot extends prior approaches and offers complementary information for data interpretation. Additional work is needed in data visualizations for metabolomics to assist investigators in the process of understanding and convey large-scale analysis results effectively, feasibly, and practically. PMID: 31269707 [PubMed]

Related Articles Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts. Metabolites. 2019 Jul 02;9(7): Authors: Laíns I, Chung W, Kelly RS, Gil J, Marques M, Barreto P, Murta JN, Kim IK, Vavvas DG, Miller JB, Silva R, Lasky-Su J, Liang L, Miller JW, Husain D Abstract The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition. PMID: 31269701 [PubMed]

Related Articles The Search for Clinically Useful Biomarkers of Complex Disease: A Data Analysis Perspective. Metabolites. 2019 Jul 02;9(7): Authors: Considine EC Abstract Unmet clinical diagnostic needs exist for many complex diseases, which (it is hoped) will be solved by the discovery of metabolomics biomarkers. However, at present, no diagnostic tests based on metabolomics have yet been introduced to the clinic. This review is presented as a research perspective on how data analysis methods in metabolomics biomarker discovery may contribute to the failure of biomarker studies and suggests how such failures might be mitigated. The study design and data pretreatment steps are reviewed briefly in this context, and the actual data analysis step is examined more closely. PMID: 31269649 [PubMed]

Related Articles Comparison of Retention Behavior between Supercritical Fluid Chromatography and Normal-Phase High-Performance Liquid Chromatography with Various Stationary Phases. Molecules. 2019 Jul 02;24(13): Authors: Hirose T, Keck D, Izumi Y, Bamba T Abstract The retention behavior of a wide variety of stationary phases was compared in supercritical fluid chromatography (SFC) and normal-phase high-performance liquid chromatography (NP-HPLC). We also attempted to elucidate the retention behavior in SFC by investigating the selectivity of the different stationary phases. SFC separation conditions with polar stationary phases, such as silica gel (SL) and diol (Diol) phases, operate via adsorptions that include hydrophilic and ionic interactions similar to those in NP-HPLC. Moreover, non-polar stationary phases, such as pentabromophenyl (PBr), pyrenylethyl (PYE), and octadecyl (C18), could be used despite the non-polar mobile phase conditions, because the dispersion and π-π interactions were stronger in SFC than in HPLC. These results reflect the selectivity of the stationary phase and its retention factor, thus providing useful information for the selection of appropriate stationary phases for particular analytes. PMID: 31269632 [PubMed - in process]

Related Articles A Metal-Polyphenol Network Coated Nanotheranostic System for Metastatic Tumor Treatments. Small. 2017 12;13(48): Authors: Fan JX, Zheng DW, Mei WW, Chen S, Chen SY, Cheng SX, Zhang XZ Abstract As a characteristic trait of most tumor types, metastasis is the major cause of the death of patients. In this study, a photothermal agent based on gold nanorod is coated with metal (Gd3+ )-organic (polyphenol) network to realize combination therapy for metastatic tumors. This nanotheranostic system significantly enhances antitumor therapeutic effects in vitro and in vivo with the combination of photothermal therapy (PTT) and chemotherapy, also can remarkably prevent the invasion and metastasis due to the presence of polyphenol. After the treatment, an 81% decrease in primary tumor volumes and a 58% decrease in lung metastasis are observed. In addition, the good performance in magnetic resonance imaging, computerized tomography, and photothermal imaging of the nanotheranostic system can realize image-guided therapy. The multifunctional nanotheranostic system will find a great potential in diagnosis and treatment integration in tumor treatments, and broaden the applications of PTT treatment. PMID: 29125688 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology. Stem Cells Transl Med. 2017 01;6(1):31-39 Authors: Sato Y, Kobayashi H, Higuchi T, Shimada Y, Ida H, Ohashi T Abstract Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α-glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late-onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle. However, the disease mechanism underlying PD cardiomyopathy is not fully understood. Several researchers have shown that PD induced pluripotent stem cell (iPSC)-derived cardiomyocytes successfully replicate the disease phenotype and are useful disease models. We have analyzed the metabolomic profile of late-onset PD iPSC-derived cardiomyocytes and found that oxidative stress and mitochondrial dysfunction are likely associated with cardiac complications. Furthermore, we have validated that these disease-specific changes were also observed in the cardiomyocytes and skeletal muscle of a genetically engineered murine PD model. Oxidative stress may contribute to skeletal muscle and cardiomyocyte dysfunction in PD mice; however, NF-E2-related factor 2 was downregulated in cardiomyocytes and skeletal muscle, despite evidence of oxidative stress. We hypothesized that oxidative stress and an impaired antioxidative stress response mechanism may underlie the molecular pathology of late-onset PD. Stem Cells Translational Medicine 2017;6:31-39. PMID: 28170191 [PubMed - indexed for MEDLINE]

Macrophages and Metabolism in the Tumor Microenvironment. Cell Metab. 2019 Jul 02;30(1):36-50 Authors: Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L Abstract Tumor-associated macrophages (TAMs) constitute a plastic and heterogeneous cell population of the tumor microenvironment (TME) that can account for up to 50% of some solid neoplasms. Most often, TAMs support disease progression and resistance to therapy by providing malignant cells with trophic and nutritional support. However, TAMs can mediate antineoplastic effects, especially in response to pharmacological agents that boost their phagocytic and oxidative functions. Thus, TAMs and their impact on the overall metabolic profile of the TME have a major influence on tumor progression and resistance to therapy, de facto constituting promising targets for the development of novel anticancer agents. Here, we discuss the metabolic circuitries whereby TAMs condition the TME to support tumor growth and how such pathways can be therapeutically targeted. PMID: 31269428 [PubMed - in process]

Cell-Based Metabolomics for Untargeted Screening and Prioritization of Vertebrate-Active Stressors in Streams Across the United States. Environ Sci Technol. 2019 Jul 03;: Authors: Collette TW, Ekman D, Zhen H, Nguyen H, Bradley PM, Teng Q Abstract The U.S. Geological Survey and the U.S. Environmental Protection Agency have assessed contaminants in 38 streams across the U.S., using an extensive suite of target-chemical analysis methods along with a variety of biological effects tools. Here we report zebrafish liver (ZFL) cell-culture based NMR metabolomic analysis of these split stream samples. We used this untargeted approach to evaluate the sites according to overall impact on the ZFL metabolome and found that neither the total number of organics detected at the sites, nor their cumulative concentrations, were good predictors of these impacts. Further, we used partial-least squares regression to compare ZFL endogenous metabolite profiles to values for 455 potential stressors (organics, inorganics, and physical properties) measured in these waters and found that the profiles covaried with at most 280 of the stressors, which were subsequently ranked into quartiles based on the strength of their covariance. While contaminants of emerging concern (CECs) were well represented in the top, most strongly, covarying quartile - suggesting considerable potential for eliciting biological responses at these sites - there was even higher representation of various well-characterized legacy contaminants (e.g., PCBs). These results emphasize the importance of complementing chemical analysis with untargeted bioassays to help focus regulatory efforts on the most significant ecosystem threats. PMID: 31268696 [PubMed - as supplied by publisher]

A Digital Method to Quantify Type I IFN. J Interferon Cytokine Res. 2019 Jul 03;: Authors: Rius-Rocabert S, Presa JL, Esteban-Rubio S, Ayuso-Sacido A, Nistal-Villan E Abstract Interferon (IFN), the first ever-described cytokine, has a potent activity against viruses. Soon since its discovery, quantification of IFN has been an important issue. Most of the traditional methods to measure IFN biological activity rely on indirect methods that quantify dyes retained by IFN-protected cells against a lytic virus, or by techniques that indirectly quantify viral replication by measuring the expression level of viral-encoded reporter proteins such as the green fluorescent protein (GFP). In both cases, the IFN units are determined by the quantification of an effective dose 50, defined as the IFN dose that prevents 50% cell death of 50% reduction of the maximal amount of GFP intensity. In this study we propose the use of an alternative approach to measure IFN activity by calculating the minimal IFN dose 50 as the amount of IFN able to completely protect 50% of the cells from infection measured by the total absence of virus-dependent GFP signal in a cell culture plate. This sensitive approach could be used to easily quantify the Z value to determine IFN bioassay robustness. We believe that this approximation could be interesting to be considered by the IFN community. PMID: 31268382 [PubMed - as supplied by publisher]

Mitochondrial activity contributes to impaired renal metabolic homeostasis and renal pathology in STZ-induced diabetic mice. Am J Physiol Renal Physiol. 2019 Jul 03;: Authors: Wu M, Li S, Yu X, Chen W, Ma H, Shao C, Zhang Y, Zhang A, Huang S, Jia Z Abstract Diabetic nephropathy (DN) has become the main cause of end-stage renal disease worldwide while the efficacy of current therapeutic strategies on DN remains unsatisfactory. Recent researches reported the involvement of metabolic re-arrangement in the pathological process of DN, and of all the disturbances in metabolism, mitochondria serve as key regulatory hubs. In the present study, high-resolution mass spectrometry-based none-target metabolomics was employed to uncover the metabolic characteristics of early diabetic kidney with or without the inhibition of mitochondrial activity. At first, we observed a moderate enhancement of mitochondrial complex-1 activity in diabetic kidney, which was completely normalized by a specific mitochondrial complex-1 inhibitor rotenone (ROT). Meanwhile, metabolomics data indicated over-activated pentose phosphate pathway, purine and pyrimidine metabolism, hexosamine biosynthetic pathway, and Kreb cycle, which were strikingly corrected by ROT. In addition, ROT also strikingly corrected imbalanced redox homeostasis possibly by increasing the ratio of antioxidant metabolites GSH and NAPDH against their oxidative form. In agreement with the improved metabolic status and oxidative response, ROT attenuated glomerular and tubular injury efficiently. The fibrotic markers (fibronectin, α-SMA, collagen I and collagen III), inflammatory factors (TNF-ᵯC;, IL-1ᵯD;, and ICAM-1) and oxidative stress were all markedly blocked by ROT. In vitro, ROT dose-dependently attenuated high glucose-induced proliferation and extracellular matrix production in mesangial cells. Collectively, these findings revealed that the overactivation of mitochondrial activity in kidney could contribute to the metabolic disorders and the pathogenesis of early diabetic nephropathy. PMID: 31268353 [PubMed - as supplied by publisher]

The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor? Ann Oncol. 2019 Jul 03;: Authors: Elkrief A, Derosa L, Kroemer G, Zitvogel L, Routy B Abstract Immune checkpoint inhibitors (ICI) now represent the standard of care for several cancer types. In pre-clinical models, absence of an intact gut microbiome negatively impacted ICI efficacy and these findings permitted to unravel the importance of the commensal microbiota in immuno-oncology. Recently, multiple clinical studies including more than 1800 patients in aggregate demonstrated the negative predictive impact of treatments with broad-spectrum antibiotics (ATB) on cancer patients receiving ICI. Altogether, these results have led to the hypothesis that ATB-induced symbiosis might influence the clinical response through the modulation of the gut microbiome. Controversy still remains, as ATB treatment might simply constitute a surrogate marker of unfit or immunodeficient patients. In this review, we summarize recent publications addressing the impact of the gut microbiome on ICI efficacy, discuss currently available data on the effect of ATB administered in different time-frames respect to ICI initiation, and finally evoke the therapeutic implications of these findings. PMID: 31268133 [PubMed - as supplied by publisher]

Triterpenoids Extracted from Rhus chinensis Mill Act Against Colorectal Cancer by Inhibiting Enzymes in Glycolysis and Glutaminolysis: Network Analysis and Experimental Validation. Nutr Cancer. 2019 Jul 03;:1-27 Authors: Wang G, Wang YZ, Yu Y, Wang JJ, Yin PH, Xu K Abstract Background: Rhus chinensis Mill is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of R. chinensis such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking. Study Design: Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from R. chinensis. In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods. Results: Our results showed that the total TER in R. chinensis remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways. Conclusion: Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from R. chinensis, mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification. PMID: 31267795 [PubMed - as supplied by publisher]

Related Articles Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability. EMBO Rep. 2019 Jul;20(7):e47352 Authors: Ravichandran R, Kodali K, Peng J, Potts PR Abstract Melanoma antigen genes (MAGEs) are emerging as important oncogenic drivers that are normally restricted to expression in male germ cells but are aberrantly expressed in cancers and promote tumorigenesis. Mechanistically, MAGEs function as substrate specifying subunits of E3 ubiquitin ligases. Thus, the activation of germline-specific genes in cancer can drive metabolic and signaling pathways through altered ubiquitination to promote tumorigenesis. However, the mechanisms regulating MAGE expression and activity are unclear. Here, we describe how the MAGE-A3/6 proteins that function as repressors of autophagy are downregulated in response to nutrient deprivation. Short-term cellular starvation promotes rapid MAGE-A3/6 degradation in a proteasome-dependent manner. Proteomic analysis reveals that degradation of MAGE-A3/6 is controlled by the CRL4-DCAF12 E3 ubiquitin ligase. Importantly, the degradation of MAGE-A3/6 by CRL4-DCAF12 is required for starvation-induced autophagy. These findings suggest that oncogenic MAGEs can be dynamically controlled in response to stress to allow cellular adaptation, autophagy regulation, and tumor growth and that CRL4-DCAF12 activity is responsive to nutrient status. PMID: 31267705 [PubMed - in process]

Related Articles Phytochelatin database: a resource for phytochelatin complexes of nutritional and environmental metals. Database (Oxford). 2019 Jan 01;2019: Authors: Dennis KK, Uppal K, Liu KH, Ma C, Liang B, Go YM, Jones DP Abstract Phytochelatins (PyCs) are a diverse set of plant compounds that chelate metals, protect against metal toxicity and function in metal homeostasis. PyCs are present in plants consumed as food by humans and could, in principle, impact absorption and utilization of essential and toxic metals such as selenium and cadmium, respectively. PyCs vary in terminal amino acid composition and chain length, exist in multiple oxidation states and reversibly bind multiple metals; consequently, PyCs include a large set of possible structures. Although individual PyC-metal complexes have been studied, no resource exists to characterize the diversity of PyCs and PyC-metal complexes. We used the scientific literature to develop a database of elemental formulas for polymer forms varying in chain length from 2 to 11 glutamyl-cysteine repeats. Using elemental formulas, we calculated monoisotopic masses using the most abundant isotopes of each element and calculated masses for complexes with 13 metals of nutritional and toxicological significance. The resulting phytochelatin database (PyCDB) contains 46 260 unique elemental formulas for PyC and PyC-metal complexes. The database is available online for download as well as for direct mass queries for mass spectrometry using an accurate mass annotation tool for user-selected PyC types, metals and adducts of interest. We performed studies of a commonly consumed food-onion-to validate the database and test utility of the tool. Onion samples were analyzed using ultra-high resolution mass spectrometry-based metabolomics. Mass spectral features were annotated using the PyCDB web tool and the R package, xMSannotator; annotated features were further validated by collision-induced dissociation mass spectrometry. The results establish use and a workflow for PyCDB as a resource for characterization of PyCs and PyC-metal complexes. PMID: 31267134 [PubMed - in process]

Related Articles Metabolic regulatory oscillations in intertidal green seaweed Ulva lactuca against tidal cycles. Sci Rep. 2017 11 27;7(1):16430 Authors: Gupta V, Kushwaha HR Abstract The survival of wetland plant species largely relies on physiological adaptations essential for submergence and desiccation. Intertidal seaweeds, unlike terrestrial plants, have unique adaptations to submergence and can also sustain desiccation arising from tidal rhythms. This study determined the differential metabolic regulations in the inter-tidal seaweed species Ulva lactuca against the submergence and desiccation. During desiccation, the relative water content of the algal thalli declined with concomitant increase in reactive oxygen species (ROS) and lipid peroxidation. Nevertheless, the trends reversed during recovery on re-submergence and attained homeostasis. Metabolite profiling of U. lactuca revealed desiccation induced balance in energy reserve utilization by adjusting carbohydrate metabolism and switch over to ammonia metabolism. Upon re-submergence, thalli showed an increase in fermentative metabolites, pyruvate-alanine conversion, and the GABA shunt. Prolonged submergence induced substrate level phosphorylation mediated sugar biosynthesis while continuing the alternative carbon flux through fermentative metabolism, an increase in osmoprotectants glycine and betaine, sulfur bearing compounds cysteine and hypotaurine, and phenolic compound coniferaldehyde. The determined metabolic regulations in U. lactuca for submergence tolerance provide insights into potential evolutionarily conserved protective mechanisms across the green lineage and also highlights the possible role of sulfur oxoforms as strong free radical scavengers. PMID: 29180713 [PubMed - indexed for MEDLINE]

Related Articles Transcriptome and metabolite analyses reveal the complex metabolic genes involved in volatile terpenoid biosynthesis in garden sage (Salvia officinalis). Sci Rep. 2017 11 22;7(1):16074 Authors: Ali M, Li P, She G, Chen D, Wan X, Zhao J Abstract A large number of terpenoid compounds have been extracted from different tissues of S. officinalis. However, the molecular genetic basis of terpene biosynthesis pathways is virtually unknown. In this study, approximately 6.6 Gb of raw data were generated from the transcriptome of S. officinalis leaves using Illumina HiSeq 2000 sequencing. After filtering and removing the adapter sequences from the raw data, the number of reads reached 21 million, comprising 98 million of high-quality nucleotide bases. 48,671 unigenes were assembled de novo and annotated for establishing a valid database for studying terpenoid biosynthesis. We identified 135 unigenes that are putatively involved in terpenoid metabolism, including 70 mevalonate and methyl-erythritol phosphate pathways, terpenoid backbone biosynthesis genes, and 65 terpene synthase genes. Moreover, five terpene synthase genes were studied for their functions in terpenoid biosynthesis by using transgenic tobacco; most transgenic tobacco plants expressing these terpene synthetic genes produced increased amounts of terpenoids compared with wild-type control. The combined data analyses from the transcriptome and metabolome provide new insights into our understanding of the complex metabolic genes in terpenoid-rich sage, and our study paves the way for the future metabolic engineering of the biosynthesis of useful terpene compounds in S. officinalis. PMID: 29167468 [PubMed - indexed for MEDLINE]