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Metabolic reprogramming

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https://www.readbyqxmd.com/read/29054798/the-antimicrobial-peptide-nisin-z-induces-selective-toxicity-and-apoptotic-cell-death-in-cultured-melanoma-cells
#1
Angélique Lewies, Johannes Frederik Wentzel, Hayley van Dyk, Lissinda Hester Du Plessis
Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells present with altered energy metabolism which is associated with elevated reactive oxygen species (ROS) generation. This is also evident for melanoma, the leading cause of skin cancer related deaths. Altered mechanisms affecting mitochondrial bioenergetics pose attractive targets for novel anti-cancer therapies...
October 17, 2017: Biochimie
https://www.readbyqxmd.com/read/29054472/the-mitochondrial-respiratory-chain-a-metabolic-rheostat-of-innate-immune-cell-mediated-antibacterial-responses
#2
REVIEW
Leif E Sander, Johan Garaude
Upon microbial infection, cells of the innate immune system undergo profound metabolic reprogramming in order to eradicate pathogens, promote inflammation, and eventually restore tissue homeostasis. Mitochondria are at the core of these adaptations, given their dual role as metabolic hubs and innate immune signaling platforms. The mitochondrial electron transport chain (ETC) is very well characterized at the genetic, molecular, structural, and biochemical level. In contrast, the role for mitochondrial ETC and metabolites beyond fulfilling cellular ATP synthesis in innate immune cell biology was not understood until recently...
October 17, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29051502/comparative-transcriptomics-reveal-developmental-turning-points-during-embryogenesis-of-a-hemimetabolous-insect-the-damselfly-ischnura-elegans
#3
Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R Brugler, M Eric Schranz, Heike Hadrys, George Amato, Rob DeSalle
Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051490/computational-design-of-small-transcription-activating-rnas-for-versatile-and-dynamic-gene-regulation
#4
James Chappell, Alexandra Westbrook, Matthew Verosloff, Julius B Lucks
A longstanding goal of synthetic biology has been the programmable control of cellular functions. Central to this is the creation of versatile regulatory toolsets that allow for programmable control of gene expression. Of the many regulatory molecules available, RNA regulators offer the intriguing possibility of de novo design-allowing for the bottom-up molecular-level design of genetic control systems. Here we present a computational design approach for the creation of a bacterial regulator called Small Transcription Activating RNAs (STARs) and create a library of high-performing and orthogonal STARs that achieve up to ~ 9000-fold gene activation...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051480/nox4-functions-as-a-mitochondrial-energetic-sensor-coupling-cancer-metabolic-reprogramming-to-drug-resistance
#5
Karthigayan Shanmugasundaram, Bijaya K Nayak, William E Friedrichs, Dharam Kaushik, Ronald Rodriguez, Karen Block
The molecular mechanisms that couple glycolysis to cancer drug resistance remain unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform, NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We find that NOX4 localizes to the inner mitochondria membrane and that subcellular redistribution of ATP levels from the mitochondria act as an allosteric switch to activate NOX4. We provide evidence that NOX4-derived reactive oxygen species (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2)...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#6
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047090/metabolic-reprogramming-and-redox-signaling-in-pulmonary-hypertension
#7
Lydie Plecitá-Hlavatá, Angelo D'alessandro, Karim El Kasmi, Min Li, Hui Zhang, Petr Ježek, Kurt R Stenmark
Pulmonary hypertension is a complex disease of the pulmonary vasculature, which in severe cases terminates in right heart failure. Complex remodeling of pulmonary arteries comprises the central issue of its pathology. This includes extensive proliferation, apoptotic resistance and inflammation. As such, the molecular and cellular features of pulmonary hypertension resemble hallmark characteristics of cancer cell behavior. The vascular remodeling derives from significant metabolic changes in resident cells, which we describe in detail...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046261/cinnamaldehyde-induces-fat-cell-autonomous-thermogenesis-and-metabolic-reprogramming
#8
Juan Jiang, Margo P Emont, Heejin Jun, Xiaona Qiao, Jiling Liao, Dong-Il Kim, Jun Wu
OBJECTIVE: Cinnamaldehyde (CA) is a food compound that has previously been observed to be protective against obesity and hyperglycemia in mouse models. In this study, we aimed to elucidate the mechanisms behind this protective effect by assessing the cell-autonomous response of primary adipocytes to CA treatment. METHODS: Primary murine adipocytes were treated with CA and thermogenic and metabolic responses were assessed after both acute and chronic treatments. Human adipose stem cells were differentiated and treated with CA to assess whether the CA-mediated signaling is conserved in humans...
September 1, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29042548/human-mesenchymal-stromal-cells-transplanted-into-mice-stimulate-renal-tubular-cells-and-enhance-mitochondrial-function
#9
Luca Perico, Marina Morigi, Cinzia Rota, Matteo Breno, Caterina Mele, Marina Noris, Martino Introna, Chiara Capelli, Lorena Longaretti, Daniela Rottoli, Sara Conti, Daniela Corna, Giuseppe Remuzzi, Ariela Benigni
Mesenchymal stromal cells (MSCs) are renoprotective and drive regeneration following injury, although cellular targets of such an effect are still ill-defined. Here, we show that human umbilical cord (UC)-MSCs transplanted into mice stimulate tubular cells to regain mitochondrial mass and function, associated with enhanced microtubule-rich projections that appear to mediate mitochondrial trafficking to create a reparative dialogue among adjacent tubular cells. Treatment with UC-MSCs in mice with cisplatin-induced acute kidney injury (AKI) regulates mitochondrial biogenesis in proximal tubuli by enhancing PGC1α expression, NAD(+) biosynthesis and Sirtuin 3 (SIRT3) activity, thus fostering antioxidant defenses and ATP production...
October 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29042482/resveratrol-stimulates-the-metabolic-reprogramming-of-human-cd4-t-cells-to-enhance-effector-function
#10
Marco Craveiro, Gaspard Cretenet, Cédric Mongellaz, Maria I Matias, Olivier Caron, Maria C Pedroso de Lima, Valérie S Zimmermann, Eric Solary, Valérie Dardalhon, Vjekoslav Dulić, Naomi Taylor
The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4(+) T cells showed defective antigen receptor signaling and arrest at the G1 stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia-mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest...
October 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/29042306/cigarette-smoke-induces-mitochondrial-metabolic-reprogramming-in-lung-cells
#11
Hitendra S Solanki, Niraj Babu, Ankit Jain, Mohd Younis Bhat, Vinuth N Puttamallesh, Jayshree Advani, Remya Raja, Kiran K Mangalaparthi, Mahesh M Kumar, T S Keshava Prasad, Premendu Prakash Mathur, David Sidransky, Harsha Gowda, Aditi Chatterjee
Cellular transformation owing to cigarette smoking is due to chronic exposure and not acute. However, systematic studies to understand the molecular alterations in lung cells due to cigarette smoke are lacking. To understand these molecular alterations induced by chronic cigarette smoke exposure, we carried out tandem mass tag (TMT) based temporal proteomic profiling of lung cells exposed to cigarette smoke upto 12months. We identified 2620 proteins in total, of which 671 proteins were differentially expressed (1...
October 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29039000/transcriptional-and-posttranscriptional-regulation-of-drought-stress-treatments-in-brachypodium-leaves
#12
Edoardo Bertolini, Mario Enrico Pè, Erica Mica
Plant sensing drought stress conditions activate complex molecular networks leading to a rapid reprogramming of plant physiology and metabolism, in order to survive in suboptimal conditions.Here, we describe a standardized in vivo soil drought assay to investigate the effects of drought stress on leaf growth. Since it is now clear that stress responses can be specific to developmental stages and cell types, we describe a procedure to dissect the leaf in three distinct areas in order to study transcriptional and posttranscriptional gene regulation on both organ and cellular levels...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29038547/a-novel-fer-fert-targeting-compound-selectively-evokes-metabolic-stress-and-necrotic-death-in-malignant-cells
#13
Yoav Elkis, Moshe Cohen, Etai Yaffe, Shirly Satmary-Tusk, Tal Feldman, Elad Hikri, Abraham Nyska, Ariel Feiglin, Yanay Ofran, Sally Shpungin, Uri Nir
Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29035842/derivation-and-characterization-of-integration-free-ipsc-line-isrm-um51-derived-from-six2-positive-renal-cells-isolated-from-urine-of-an-african-male-expressing-the-cyp2d6-4-17-variant-which-confers-intermediate-drug-metabolizing-activity
#14
Martina Bohndorf, Audrey Ncube, Lucas-Sebastian Spitzhorn, Jürgen Enczmann, Wasco Wruck, James Adjaye
SIX2-positive renal cells isolated from urine from a 51year old male of African origin bearing the CYP2D6 *4/*17 variant were reprogrammed by nucleofection of a combination of two episomal-based plasmids omitting pathway (TGFβ, MEK and GSK3β) inhibition. The induced pluripotent stem cells (iPSCs) were characterized by immunocytochemistry, embryoid body formation, DNA-fingerprinting and karyotype analysis. Comparative transcriptome analyses with human embryonic stem cell lines H1 and H9 revealed a Pearson correlation of 0...
October 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29035781/lack-of-myeloid-fatp1-increases-atherosclerotic-lesion-size-in-ldlr-mice
#15
Liyang Zhao, Alyssa J Cozzo, Amy R Johnson, Taylor Christensen, Alex J Freemerman, James E Bear, Jeremy D Rotty, Brian J Bennett, Liza Makowski
BACKGROUND AND AIMS: Altered metabolism is an important regulator of macrophage (MΦ) phenotype, which contributes to inflammatory diseases such as atherosclerosis. Broadly, pro-inflammatory, classically-activated MΦs (CAM) are glycolytic while alternatively-activated MΦs (AAM) oxidize fatty acids, although overlap exists. We previously demonstrated that MΦ fatty acid transport protein 1 (FATP1, Slc27a1) was necessary to maintain the oxidative and anti-inflammatory AAM phenotype in vivo in a model of diet-induced obesity...
October 7, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29035280/adipocyte-cannabinoid-receptor-cb1-regulates-energy-homeostasis-and-alternatively-activated-macrophages
#16
Inigo Ruiz de Azua, Giacomo Mancini, Raj Kamal Srivastava, Alejandro Aparisi Rey, Pierre Cardinal, Laura Tedesco, Cristina Maria Zingaretti, Antonia Sassmann, Carmelo Quarta, Claudia Schwitter, Andrea Conrad, Nina Wettschureck, V Kiran Vemuri, Alexandros Makriyannis, Jens Hartwig, Maria Mendez-Lago, Laura Bindila, Krisztina Monory, Antonio Giordano, Saverio Cinti, Giovanni Marsicano, Stefan Offermanns, Enzo Nisoli, Uberto Pagotto, Daniela Cota, Beat Lutz
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29034893/establishment-of-dyt5-patient-specific-induced-pluripotent-stem-cells-with-a-gch1-mutation
#17
Nagahisa Murakami, Taizo Ishikawa, Takayuki Kondo, Keiko Imamura, Kayoko Tsukita, Takako Enami, Misato Funayama, Ran Shibukawa, Shinichi Matsumoto, Yuishin Izumi, Etsuro Ohta, Fumiya Obata, Ryuji Kaji, Haruhisa Inoue
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 20-year-old dystonia patient with a GCH1 mutation (DYT5). Episomal vectors were used to introduce reprogramming factors (OCT3/4, SOX2, KLF4, L-MYC, LIN28, and p53 carboxy-terminal dominant-negative fragment) to the PBMCs. The generated iPSCs expressed pluripotency markers, and were capable of differentiating into derivates of all three germ layers in vitro. The iPSC line also showed a normal karyotype and preserved the GCH1 mutation...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29030115/store-operated-ca-2-entry-controls-clonal-expansion-of-t-cells-through-metabolic-reprogramming
#18
Martin Vaeth, Mate Maus, Stefan Klein-Hessling, Elizaveta Freinkman, Jun Yang, Miriam Eckstein, Scott Cameron, Stuart E Turvey, Edgar Serfling, Friederike Berberich-Siebelt, Richard Possemato, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca(2+)-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29028873/mirna-in-tumour-metabolism-and-why-could-it-be-the-preferred-pathway-for-energy-reprograming
#19
Aliaa A Alamoudi, Amina Alnoury, Hoda Gad
The current literature on the role of microRNA (miRNA) in tumour metabolism is growing, and a number of studies regularly confirm the impact miRNA can have in energy reprograming in tumours. However, there remains to be a lack of understanding of the larger perspective of the role of miRNA in the metabolism story. In the first part of this review, we provide a comprehensive and up-to-date description of the extensive role of miRNAs in tumour metabolism including glucose, lipid and amino acid metabolism. However, in the second part, we aim to provide a description of the multidimensional role miRNA can be playing in tumour metabolism...
September 23, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29025968/activation-of-ampk-mtorc1-mediated-autophagy-by-metformin-reverses-clk1-deficiency-sensitized-dopaminergic-neuronal-death
#20
Qiuting Yan, Chaojun Han, Guanghui Wang, John L Waddington, Longtai Zheng, Xuechu Zhen
The autophagy-lysosome pathway (ALP) plays a critical role in the pathology of Parkinson's disease (PD). Clk1 (coq7) is a mitochondrial hydroxylase that is essential for Coenzyme Q (ubiquinone) biosynthesis. We have reported previously that Clk1 regulates microglia activation via modulating microglia metabolic reprogramming, which contributes to dopaminergic neuronal survival. This study explored the direct effect of Clk1 on dopaminergic neuronal survival. We demonstrated that Clk1 deficiency inhibited dopaminergic neuronal autophagy in cultured MN9D dopaminergic neurons and in SNc of Clk+/- mutant mice and consequently sensitized dopaminergic neuron damage and behavioral defects...
October 12, 2017: Molecular Pharmacology
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