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metabolism reprogramming

Lanyu Li, Dandan Zhang, Yanyan Ren, Sheng Ye, Beibei Zheng, Shulin Liu, Jam Zaheer Ahmed, Mengmei Li, Deshun Shi, Ben Huang
In recent years, induced pluripotent stem cells (iPSCs) technique is able to allow us to generate pluripotency from somatic cells in vitro through the over expression of several transcription factors. Normally, viral vectors and transcription factors are commonly used on iPSC technique, which could cause many barriers on further application. In this study, we attempt to process a new method to obtain pluripotency from goat somatic cells in vitro under fully chemically defined condition. The results showed that chemically induced pluripotent stem cells-like cells (CiPSC-like cells) colonies were generated from goat ear fibroblasts by fully small-molecule compounds...
August 11, 2018: Reproduction in Domestic Animals, Zuchthygiene
Jolie R Schafer, Travis C Salzillo, Nitin Chakravarti, Meisam Naeimi Kararoudi, Prashant Trikha, Jennifer A Foltz, Ruoning Wang, Shulin Li, Dean A Lee
The mechanism by which natural killer (NK) cell education results in licensed NK cells with heightened effector function against missing-self targets is not known. We found that licensed human NK cells are higher in number in peripheral blood and proliferate more in vitro than unlicensed NK cells. Using high-throughput protein analysis, we found that unstimulated licensed NK cells have increased expression of the glycolytic enzyme PKM2, and after KIR crosslinking have increased phosphorylation of the metabolic modulators p38-α and AMPKα...
August 7, 2018: Journal of Allergy and Clinical Immunology
Xiaoyu Guo, Dongfeng Liu, Kang Chong
To survive under cold temperatures plants must be able to perceive a cold signal and transduce it into downstream components that induce appropriate defense mechanisms. In addition to inducing adaptive defenses, such as the production of osmotic factors to prevent freezing and the reprogramming of transcriptional pathways, cold temperatures induce changes in plant growth and development which can affect the plant life cycle. In this review, we summarize recent progress in characterizing cold-related genes and the pathways that allow transduction of the cold signal in plants, focusing primarily on studies in Arabidopsis thaliana and rice (Oryza sativa)...
August 10, 2018: Journal of Integrative Plant Biology
Mingzuo Jiang, Bing Xu, Xiaowei Li, Yulong Shang, Yi Chu, Weijie Wang, Di Chen, Nan Wu, Sijun Hu, Song Zhang, Mengbin Li, Kaichun Wu, Xiaoyong Yang, Jie Liang, Yongzhan Nie, Daiming Fan
Advanced colorectal cancer (CRC) is one of the deadliest cancers, and the 5-year survival rate of patients with metastasis is extremely low. The epithelial-mesenchymal transition (EMT) is considered essential for metastatic CRC, but the fundamental molecular basis underlying this effect remains unknown. Here, we identified that O-GlcNAcylation, a unique posttranslational modification (PTM) involved in cancer metabolic reprogramming, increased the metastatic capability of CRC. The levels of O-GlcNAcylation were increased in the metastatic CRC tissues and cell lines, which likely promoted the EMT by enhancing EZH2 protein stability and function...
August 9, 2018: Oncogene
Hsiu-Chi Lee, Shih-Chieh Lin, Meng-Hsing Wu, Shaw-Jenq Tsai
Endometriosis is a common gynecological disease, which is defined as the growth of endometrial tissues outside the uterine cavity. It often causes dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility in reproductive-age women. However, the pathogenesis of endometriosis remains largely unclear. Since our previous study revealed that ectopic endometriotic stromal cells experience greater hypoxic stress than their eutopic counterparts, we aim to investigate whether the metabolic properties are changed in the ectopic endometriotic stromal cell when compared to its eutopic counterpart...
August 9, 2018: Reproductive Sciences
Mark E Pepin, Chae-Myeong Ha, David K Crossman, Silvio H Litovsky, Sooryanarayana Varambally, Joseph P Barchue, Salpy V Pamboukian, Nikolaos A Diakos, Stavros G Drakos, Steven M Pogwizd, Adam R Wende
Ischemic cardiomyopathy (ICM) is the clinical endpoint of coronary heart disease and a leading cause of heart failure. Despite growing demands to develop personalized approaches to treat ICM, progress is limited by inadequate knowledge of its pathogenesis. Since epigenetics has been implicated in the development of other chronic diseases, the current study was designed to determine whether transcriptional and/or epigenetic changes are sufficient to distinguish ICM from other etiologies of heart failure. Specifically, we hypothesize that genome-wide DNA methylation encodes transcriptional reprogramming in ICM...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Bethany R Mordhorst, Stephanie L Murphy, Martin Schauflinger, Shirley Rojas Salazar, Tieming Ji, Susanta K Behura, Kevin D Wells, Jonathan A Green, Randall S Prather
The Warburg effect is characterized by decreased mitochondrial oxidative phosphorylation and increased glycolytic flux in adequate oxygen. The preimplantation embryo has been described to have characteristics of the Warburg effect, including similar changes in gene expression and mitochondria, which are more rudimentary in appearance. We hypothesized hypoxia would facilitate anaerobic glycolysis in fibroblasts thereby promoting gene expression and media metabolite production reflecting the Warburg effect hallmarks in early embryos...
August 2018: Cellular Reprogramming
Wei-Chan Hsu, Ming-Yu Chen, Shu-Ching Hsu, Li-Rung Huang, Cheng-Yuan Kao, Wen-Hui Cheng, Chien-Hsiung Pan, Ming-Sian Wu, Guann-Yi Yu, Ming-Shiu Hung, Chuen-Miin Leu, Tse-Hua Tan, Yu-Wen Su
Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/- ), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH ) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls...
August 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kathleen A Boyle, Jonathan Van Wickle, R Blake Hill, Adriano Marchese, Balaraman Kalyanaraman, Michael B Dwinell
Mutations in the KRAS proto-oncogene are present in 50% of all colorectal cancers and are increasingly associated with chemotherapeutic resistance to frontline biologic drugs. Accumulating evidence indicates key roles for overactive KRAS mutations in the metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis in cancer cells. Here, we sought to exploit the more negative membrane potential of cancer cell mitochondria as an untapped avenue for interfering with energy metabolism in KRAS variant-containing and KRAS wild-type colorectal cancer cells...
August 7, 2018: Journal of Biological Chemistry
Hengfu Yin, Hao-Bo Guo, David J Weston, Anne M Borland, Priya Ranjan, Paul E Abraham, Sara S Jawdy, James Wachira, Gerald A Tuskan, Timothy J Tschaplinski, Stan D Wullschleger, Hong Guo, Robert L Hettich, Stephen M Gross, Zhong Wang, Axel Visel, Xiaohan Yang
BACKGROUND: Crassulacean acid metabolism (CAM) enhances plant water-use efficiency through an inverse day/night pattern of stomatal closure/opening that facilitates nocturnal CO2 uptake. CAM has evolved independently in over 35 plant lineages, accounting for ~ 6% of all higher plants. Agave species are highly heat- and drought-tolerant, and have been domesticated as model CAM crops for beverage, fiber, and biofuel production in semi-arid and arid regions. However, the genomic basis of evolutionary innovation of CAM in genus Agave is largely unknown...
August 6, 2018: BMC Genomics
Silvia Zecchini, Matteo Giovarelli, Cristiana Perrotta, Federica Morisi, Thierry Touvier, Ilaria Di Renzo, Claudia Moscheni, Maria Teresa Bassi, Davide Cervia, Marco Sandri, Emilio Clementi, Clara De Palma
Macroautophagy/autophagy is emerging as an important process in adult muscle stem cells functions: it regulates metabolic reprogramming during activation from a quiescent state, maintain stemness and prevents senescence. We now show that autophagy is specifically required for neonatal myogenesis and muscle development. Specific deletion of Atg7 in PAX7+ (paired box 7) precursors led in mice to a dwarf phenotype, with an effect restricted to the neonatal phase of muscle development. Atg7 knockdown suppressed neonatal satellite cell (nSC) proliferation and differentiation, downregulating the GH-IGF1 functions...
August 7, 2018: Autophagy
Nina Graffmann, Martina Bohndorf, Audrey Ncube, Wasco Wruck, Karl Kashofer, Kurt Zatloukal, James Adjaye
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and its prevalence increases continuously. Here, we reprogrammed fibroblasts of a high grade NAFLD patient with homozygous wildtype PNPLA3 genotype. We characterized the induced pluripotent stem cells (iPSCs) by immunocytochemistry, flow cytometry, embryoid body formation, pluritest DNA-fingerprinting, and karyotype analysis.
July 27, 2018: Stem Cell Research
Dragana Matekalo, Marijana Skorić, Tijana Nikolić, Lazar Novaković, Milana Lukić, Jelena Božunović, Neda Aničić, Biljana Filipović, Danijela Mišić
While bioactive properties of Centaurium erythraea Rafn secoiridoid glucosides (SG) are widely recognized, many aspects related to their biochemistry, metabolism and relationship to the overall plant physiology are not yet understood. Here we present for the first time an insight into the molecular background of organ-specific and genotype-dependent constitutive biosynthesis of secoiridoids in C. erythraea, by comparing chemical profiles and secoiridoid glucosides-related gene expression. Genes encoding enzymes for intermediate steps of secoiridoids biosynthesis up to secologanin have been identified by analysing transcriptomic data from C...
August 2, 2018: Phytochemistry
Gianpiero Vigani, Irene Murgia
Iron (Fe) is a cofactor required for a variety of essential redox reactions in plant metabolism. Thus, plants have developed a complex network of interacting pathways to withstand Fe deficiency, including metabolic reprogramming. This opinion aims at revisiting such reprogramming by focusing on: (i) the functional relationships of Fe-requiring enzymes (FeREs) with respect to oxygen; and (ii) the progression of FeREs engagement, occurring under Fe deficiency stress. In particular, we considered such progression of FeREs engagement as strain responses of increasing severity during the stress phases of alarm, resistance, and exhaustion...
August 1, 2018: Trends in Plant Science
Livia de Lima Thomaz, Gabriela Peron, Janine Oliveira, Larissa Camargo da Rosa, Rodolfo Thomé, Liana Verinaud
Dendritic cells (DCs) are antigen-presenting cells with the ability to activate naïve T cells and direct the adaptive cellular immune response toward a specific profile. This is important, as different pathogens demand specific "profiles" of immune responses for their elimination. Such a goal is achieved depending on the maturation/activation status of DCs by the time of antigen presentation to T cells. Notwithstanding this, recent studies have shown that DCs alter their metabolic program to accommodate the functional changes in gene expression and protein synthesis that follow antigen recognition...
July 31, 2018: International Immunopharmacology
Sydney L Campbell, Kathryn E Wellen
Nutrient-sensing mechanisms ensure that cellular activities are coordinated with nutrient availability. Recent work has established links between metabolite pools and protein post-translational modifications, as metabolites are substrates of enzymes that add or remove modifications such as acetylation, methylation, and glycosylation. Cancer cells undergo metabolic reprogramming and exhibit metabolic plasticity that allows them to survive and proliferate within the tumor microenvironment. In this article we review the evidence that, in cancer cells, nutrient availability and oncogenic metabolic reprogramming impact the abundance of key metabolites that regulate signaling and epigenetics...
August 2, 2018: Molecular Cell
Wei Sun, Stephen Y Chan
Pulmonary arterial hypertension (PAH) is a historically neglected and highly morbid vascular disease that leads to right heart failure and, in some cases, death. The molecular origins of this disease have been poorly defined, and as such, current pulmonary vasodilator therapies do not cure or reverse this disease. Although extracellular matrix (ECM) remodeling and pulmonary arterial stiffening have long been associated with end-stage PAH, recent studies have reported that such vascular stiffening can occur early in pathogenesis...
2018: Frontiers in Medicine
Hung-Jung Wang, Mamata Pochampalli, Ling-Yu Wang, June X Zou, Pei-Shan Li, Sheng-Chieh Hsu, Bi-Juan Wang, Shih-Han Huang, Ping Yang, Joy C Yang, Cheng-Ying Chu, Chia-Ling Hsieh, Shian-Ying Sung, Chien-Feng Li, Clifford G Tepper, David K Ann, Allen C Gao, Christopher P Evans, Yoshihiro Izumiya, Chi-Pin Chuu, Wen-Ching Wang, Hong-Wu Chen, Hsing-Jien Kung
During the evolution into castration or therapy resistance, prostate cancer cells reprogram the androgen responses to cope with the diminishing level of androgens, and undergo metabolic adaption to the nutritionally deprived and hypoxia conditions. AR (androgen receptor) and PKM2 (pyruvate kinase M2) have key roles in these processes. We report in this study, KDM8/JMJD5, a histone lysine demethylase/dioxygnase, exhibits a novel property as a dual coactivator of AR and PKM2 and as such, it is a potent inducer of castration and therapy resistance...
August 2, 2018: Oncogene
Marie Liebmann, Stephanie Hucke, Kathrin Koch, Melanie Eschborn, Julia Ghelman, Achmet I Chasan, Shirin Glander, Martin Schädlich, Meike Kuhlencord, Niklas M Daber, Maria Eveslage, Marc Beyer, Michael Dietrich, Philipp Albrecht, Monika Stoll, Karin B Busch, Heinz Wiendl, Johannes Roth, Tanja Kuhlmann, Luisa Klotz
T cells critically depend on reprogramming of metabolic signatures to meet the bioenergetic demands during activation and clonal expansion. Here we identify the transcription factor Nur77 as a cell-intrinsic modulator of T cell activation. Nur77-deficient T cells are highly proliferative, and lack of Nur77 is associated with enhanced T cell activation and increased susceptibility for T cell-mediated inflammatory diseases, such as CNS autoimmunity, allergic contact dermatitis and collagen-induced arthritis. Importantly, Nur77 serves as key regulator of energy metabolism in T cells, restricting mitochondrial respiration and glycolysis and controlling switching between different energy pathways...
August 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sophie M Poznanski, Nicole G Barra, Ali A Ashkar, Jonathan D Schertzer
Metabolic flux can dictate cell fate, including immune cell effector and regulatory function. The metabolic regulation of cell function is well characterized with respect to effector, memory, and regulatory T cells. This knowledge may allow for manipulation of T cell metabolic pathways that set the stage for more effective T cell therapy. Natural Killer (NK) and T-lymphocytes have complementary roles in the defense against pathogens. However, studies of NK cell metabolism are only beginning to emerge and there is comparatively little knowledge on the metabolic regulation of NK-cell activation and effector function...
July 31, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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