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https://www.readbyqxmd.com/read/28214243/synthetic-metabolic-bypass-for-a-metabolic-toggle-switch-enhances-acetyl-coa-supply-for-isopropanol-production-by-escherichia-coli
#1
Yuki Soma, Taiki Yamaji, Fumio Matsuda, Taizo Hanai
Almost all synthetic pathways for biofuel production are designed to require endogenous metabolites in glycolysis, such as phosphoenolpyruvate, pyruvate, and acetyl-CoA. However, such metabolites are also required for bacterial cell growth. To reduce the metabolic imbalance between cell growth and target chemical production, we previously constructed a metabolic toggle switch (MTS) as a conditional flux redirection tool controlling metabolic flux of TCA cycle toward isopropanol production. This approach succeeded to improve the isopropanol production titer and yield while ensuring sufficient cell growth...
February 14, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28214225/a-relay-pathway-between-arginine-and-tryptophan-metabolism-confers-immunosuppressive-properties-on-dendritic-cells
#2
Giada Mondanelli, Roberta Bianchi, Maria Teresa Pallotta, Ciriana Orabona, Elisa Albini, Alberta Iacono, Maria Laura Belladonna, Carmine Vacca, Francesca Fallarino, Antonio Macchiarulo, Stefano Ugel, Vincenzo Bronte, Federica Gevi, Lello Zolla, Auke Verhaar, Maikel Peppelenbosch, Emilia Maria Cristina Mazza, Silvio Bicciato, Yasmina Laouar, Laura Santambrogio, Paolo Puccetti, Claudia Volpi, Ursula Grohmann
Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1 (IDO1) are immunoregulatory enzymes catalyzing the degradation of l-arginine and l-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#3
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214071/lipocalin-2-a-master-mediator-of-intestinal-and-metabolic-inflammation
#4
REVIEW
Alexander R Moschen, Timon E Adolph, Romana R Gerner, Verena Wieser, Herbert Tilg
Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is released by various cell types and is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Both intestinal and metabolic inflammation, as observed in obesity and related disorders, are associated with increased LCN2 synthesis. While LCN2 in the intestinal tract regulates the composition of the gut microbiota and shows anti-inflammatory activities, it also exhibits proinflammatory activities in other experimental settings...
February 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28213921/maternal-igf1-and-igf1r-polymorphisms-and-the-risk-of-spontaneous-preterm-birth
#5
Jian-Rong He, Yu-Mian Lai, Hui-Hui Liu, Guang-Jian Liu, Wei-Dong Li, Xue-Jiao Fan, Xue-Ling Wei, Xiao-Yan Xia, Ya-Shu Kuang, Xiao-Dan Liu, Nian-Nian Chen, Jin-Hua Lu, Qiao-Zhu Chen, Wei-Bi Mai, Hui-Min Xia, Xiu Qiu
BACKGROUND: The insulin-like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population. METHOD: A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China...
February 18, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28213886/dysregulation-of-metabolic-pathways-in-a-mouse-model-of-allergic-asthma
#6
Kevin D Quinn, Michaela Schedel, Yasmeen Nkrumah-Elie, Anthony Joetham, Michael Armstrong, Charmion Cruickshank-Quinn, Richard Reisdorph, Erwin W Gelfand, Nichole Reisdorph
BACKGROUND: Asthma is a complex lung disease resulting from the interplay of genetic and environmental factors. To understand the molecular changes that occur during the development of allergic asthma without genetic and environmental confounders, an experimental model of allergic asthma in mice was used. Our goals were to (1) identify changes at the small molecule level due to allergen exposure, (2) determine perturbed pathways due to disease, and (3) determine whether small molecule changes correlate with lung function...
February 18, 2017: Allergy
https://www.readbyqxmd.com/read/28213885/epigenetic-modifier-induced-enhancement-of-fumiquinazoline-c-production-in-aspergillus-fumigatus-ga-l7-an-endophytic-fungus-from-grewia-asiatica-l
#7
Ankita Magotra, Manjeet Kumar, Manoj Kushwaha, Praveen Awasthi, Chand Raina, Ajai Prakash Gupta, Bhahwal A Shah, Sumit G Gandhi, Asha Chaubey
Present study relates to the effect of valproic acid, an epigenetic modifier on the metabolic profile of Aspergillus fumigatus (GA-L7), an endophytic fungus isolated from Grewia asiatica L. Seven secondary metabolites were isolated from A. fumigatus (GA-L7) which were identified as: pseurotin A, pseurotin D, pseurotin F2, fumagillin, tryprostatin C, gliotoxin and bis(methylthio)gliotoxin. Addition of valproic acid in the growth medium resulted in the alteration of secondary metabolic profile with an enhanced production of a metabolite, fumiquinazoline C by tenfolds...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28213823/long-term-resistance-exercise-induced-muscular-hypertrophy-is-associated-with-autophagy-modulation-in-rats
#8
Insu Kwon, Yongchul Jang, Joon-Yong Cho, Young C Jang, Youngil Lee
Elevation of anabolism and concurrent suppression of catabolism are critical metabolic adaptations for muscular hypertrophy in response to resistance exercise (RE). Here, we investigated if RE-induced muscular hypertrophy is acquired by modulating a critical catabolic process autophagy. Male Wistar Hannover rats (14 weeks old) were randomly assigned to either sedentary control (SC, n = 10) or resistance exercise (RE, n = 10). RE elicited significant hypertrophy of flexor digitorum profundus (FDP) muscles in parallel with enhancement in anabolic signaling pathways (phosphorylation of AKT, mTOR, and p70S6K)...
February 17, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28213543/functional-characterization-of-a-28-kb-catabolic-island-from-pseudomonas-sp-m1-involved-in-biotransformation-of-%C3%AE-myrcene-and-related-plant-derived-volatiles
#9
Pedro Soares-Castro, Pedro Montenegro-Silva, Hermann J Heipieper, Pedro M Santos
Pseudomonas sp. M1 is able to mineralize highly hydrophobic and recalcitrant compounds such as benzene, phenol and their methylated/halogenated derivatives, as well as the backbone of several monoterpenes. The ability to use such spectrum of compounds as sole carbon source is, most probably, associated with a genetic background evolved under different environmental constraints. The outstanding performance of M1 strain regarding β-myrcene catabolism was elucidated in this work, with focus on the biocatalytical potential of β-myrcene-associated core-code, comprised in a 28-kb genomic island (GI), predicted to be organized in 8 transcriptional units...
February 17, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28213524/g-protein-coupled-receptor-kinase-2-grk-2-regulates-serotonin-metabolism-through-the-monoamine-oxidase-amx-2-in-caenorhabditis-elegans
#10
Jianjun Wang, Jiansong Luo, Dipendra K Aryal, William C Wetzel, Richard Nass, Jeffrey L Benovic
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs) and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans. Our studies demonstrate that grk-2 loss-of-function strains are egg-laying defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213469/insulin-signaling-via-the-pi3k-akt-pathway-regulates-airway-glucose-uptake-and-barrier-function-in-a-cftr-dependent-manner
#11
Samuel A Molina, Hannah K Moriarty, Danny T Infield, Barry R Imhoff, Rachel J Vance, Agnes H Kim, Jason M Hansen, William R Hunt, Michael Koval, Nael A McCarty
Cystic fibrosis-related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Since glucose is a nutrient present in the airways of patients with bacterial airway infections and since insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by qPCR, immunoblot, immunofluorescence, and glucose uptake assays...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213390/epigenetic-patterns-in-blood-associated-with-lipid-traits-predict-incident-coronary-heart-disease-events-and-are-enriched-for-results-from-genome-wide-association-studies
#12
Åsa K Hedman, Michael M Mendelson, Riccardo E Marioni, Stefan Gustafsson, Roby Joehanes, Marguerite R Irvin, Degui Zhi, Johanna K Sandling, Chen Yao, Chunyu Liu, Liming Liang, Tianxiao Huan, Allan F McRae, Serkalem Demissie, Sonia Shah, John M Starr, L Adrienne Cupples, Panos Deloukas, Timothy D Spector, Johan Sundström, Ronald M Krauss, Donna K Arnett, Ian J Deary, Lars Lind, Daniel Levy, Erik Ingelsson
BACKGROUND: Genome-wide association studies have identified loci influencing circulating lipid concentrations in humans; further information on novel contributing genes, pathways, and biology may be gained through studies of epigenetic modifications. METHODS AND RESULTS: To identify epigenetic changes associated with lipid concentrations, we assayed genome-wide DNA methylation at cytosine-guanine dinucleotides (CpGs) in whole blood from 2306 individuals from 2 population-based cohorts, with replication of findings in 2025 additional individuals...
January 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28213331/mitochondrial-metabolism-and-energy-sensing-in-tumor-progression
#13
REVIEW
Luisa Iommarini, Anna Ghelli, Giuseppe Gasparre, Anna Maria Porcelli
Energy homeostasis is pivotal for cell fate since metabolic regulation, cell proliferation and death are strongly dependent on the balance between catabolic and anabolic pathways. In particular, metabolic and energetic changes have been observed in cancer cells even before the discovery of oncogenes and tumor suppressors, but has been neglected for a long time. Instead, during the past 20years a renaissance of the study of tumor metabolism has led to a revised and more accurate sight of the metabolic landscape of cancer cells...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#14
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213287/butein-induction-of-ho-1-by-p38-mapk-nrf2-pathway-in-adipocytes-attenuates-high-fat-diet-induced-adipose-hypertrophy-in-mice
#15
Zheng Wang, Sun-O Ka, Youngyi Lee, Byung-Hyun Park, Eun Ju Bae
Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2)...
February 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28213272/rev-erb-regulation-of-cholesterologenesis
#16
Sadichha Sitaula, Jinsong Zhang, Fernanda Ruiz, Thomas P Burris
REV-ERBα and REV-ERBβ are heme regulated nuclear receptors that are known to regulate metabolic pathways. We previously demonstrated that treatment of mice with synthetic REV-ERB agonists suppressed plasma cholesterol levels and the hepatic levels of the rate limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-Mmethylglutaryl-CoA reductase). Here, we characterize the role of REV-ERB on the cholesterol biosynthetic pathway in greater detail. The REV-ERB agonist SR9009 reduced plasma cholesterol levels in both wild type C57Bl/6 and low density lipoprotein receptor (LDLR) null mice as well as reducing the expression of an array of genes within the cholesterol biosynthetic pathway...
February 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#17
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213128/quantitative-proteomic-analysis-of-human-testis-reveals-system-wide-molecular-and-cellular-pathways-associated-with-non-obstructive-azoospermia
#18
Mehdi Alikhani, Mehdi Mirzaei, Marjan Sabbaghian, Pouria Parsamatin, Razieh Karamzadeh, Samane Adib, Niloofar Sodeifi, Mohammad Ali Sadighi Gilani, Masoud Zabet-Moghaddam, Lindsay Parker, Yunqi Wo, Vivek Gupta, Paul A Haynes, Hamid Gourabi, Hossein Baharvand, Ghasem Hosseini Salekdeh
: Male infertility accounts for half of the infertility problems experienced by couples. Azoospermia, having no measurable level of sperm in seminal fluid, is one of the known conditions resulting in male infertility. In order to elucidate the complex molecular mechanisms causing male azoospermia, label-free quantitative shotgun proteomics was carried out on testicular tissue specimens from patients with obstructive azoospermia and non-obstructive azoospermia, including maturation arrest (MA) and Sertoli cell only syndrome (SCOS)...
February 14, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28212815/systematic-testing-of-enzyme-perturbation-sensitivities-via-graded-dcas9-modulation-in-saccharomyces-cerevisiae
#19
Matthew Deaner, Hal S Alper
Dissecting genotype-phenotype relationships in a high-throughput and scalable manner is still an unresolved problem facing metabolic engineers. While the RNA-guided nuclease Cas9 has been repurposed as a programmable transcription regulator, its application has typically been limited to binary on/off regulation and thus misses informative and potentially optimal intermediate levels of gene expression. In this work, we establish a rapid method for fine-tuned, graded expression of pathway enzymes via dCas9 regulation by varying sgRNA target location as the dominant parameter...
February 14, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28212728/metabolic-pathways-regulated-by-p63
#20
REVIEW
Eleonora Candi, Artem Smirnov, Emanuele Panatta, Anna Maria Lena, Flavia Novelli, Mara Mancini, Giuditta Viticchiè, Maria Cristina Piro, Nicola Di Daniele, Margherita Annicchiarico-Petruzzelli, Gerry Melino
The transcription factor p63 belongs to the p53-family and is a master regulator of proliferative potential, lineage specification, and differentiation in epithelia during development and tissue homeostasis. In cancer, p63 contribution is isoform-specific, with both oncogenic and tumour suppressive roles attributed, for ΔNp63 and TAp63, respectively. Recently, p53 and TAp73, in line with other tumour suppressor genes, have emerged as important regulators of energy metabolism and metabolic reprogramming in cancer...
January 15, 2017: Biochemical and Biophysical Research Communications
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