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Metabolic reprogramming

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https://www.readbyqxmd.com/read/28821788/bioenergetic-adaptations-in-chemoresistant-ovarian-cancer-cells
#1
Sajad Dar, Jasdeep Chhina, Ismail Mert, Dhananjay Chitale, Thomas Buekers, Hareena Kaur, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan
Earlier investigations have revealed that tumor cells undergo metabolic reprogramming and mainly derive their cellular energy from aerobic glycolysis rather than oxidative phosphorylation even in the presence of oxygen. However, recent studies have shown that certain cancer cells display increased oxidative phosphorylation or high metabolically active phenotype. Cellular bioenergetic profiling of 13 established and 12 patient derived ovarian cancer cell lines revealed significant bioenergetics diversity. The bioenergetics phenotype of ovarian cancer cell lines correlated with functional phenotypes of doubling time and oxidative stress...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821609/insulin-like-growth-factor-1-signalling-is-essential-for-mitochondrial-biogenesis-and-mitophagy-in-cancer-cells
#2
Amy Lyons, Michael Coleman, Sarah Riis, Cedric Favre, Ciara H O'Flanagan, Alexander V Zhdanov, Dmitri B Papkovsky, Stephen D Hursting, Rosemary O'Connor
Mitochondrial activity and metabolic reprogramming influence the phenotype of cancer cells and resistance to targeted therapy. We previously established that an Insulin-like Growth Factor 1 (IGF-1)-inducible mitochondrial UTP carrier (PNC1/SLC25A33) promotes cell growth. This prompted us to investigate whether IGF signaling is essential for mitochondrial maintenance in cancer cells, and whether this contributes to therapy resistance. Here, we show that IGF-1 stimulates mitochondrial biogenesis in a range of cell lines...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28819582/relationship-of-metabolic-alterations-and-pd-l1-expression-in-cisplatin-resistant-lung-cancer
#3
M Wangpaichitr, H Kandemir, Y Y Li, C Wu, Djm Nguyen, L G Feun, M T Kuo, N Savaraj
Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose...
April 28, 2017: Cell & Developmental Biology
https://www.readbyqxmd.com/read/28818477/human-imprinting-disorders-principles-practice-problems-and-progress
#4
REVIEW
Deborah J G Mackay
Epigenetic regulation orchestrates gene expression with exquisite precision, over a huge dynamic range and across developmental space and time, permitting genomically-homogeneous humans to develop and adapt to their surroundings. Every generation, these epigenetic marks are re-set twice: in the germline, to enable differentiation of sperm and eggs, and at fertilisation, to create the totipotent zygote that then begins growth and differentiation into a new human. A small group of genes evades the second, zygotic wave of epigenetic reprogramming, and these genes retain an epigenetic 'imprint' of the parent from whom they were inherited...
August 14, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28812308/transcriptional-regulation-of-the-protein-kinase-a-subunits-in-saccharomyces-cerevisiae-during-fermentative-growth
#5
Fiorella Galello, Constanza Pautasso, Sol Reca, Luciana Cañonero, Paula Portela, Silvia Moreno, Silvia Rossi
Yeast cells can adapt their growth in response to the nutritional environment. Glucose is the favorite carbon source of Saccharomyces cerevisiae that prefers a fermentative metabolism despite the presence of oxygen. When glucose is consumed, the cell switches to the aerobic metabolism of ethanol, during the so-called diauxic shift. The difference between fermentative and aerobic growth is in part mediated by a regulatory mechanism called glucose repression. During glucose derepression a profound gene transcriptional reprogramming occurs and genes involved in the utilization of alternative carbon sources are expressed...
August 15, 2017: Yeast
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#6
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrate that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation accompanied with a relative decrease in the proliferation of MUC1-overexpressing cells compared to steady state conditions...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808139/differential-expression-of-sirtuin-2-and-adipocyte-maturation-restriction-an-adaptation-process-during-hypoxia-in-fish
#7
Ekambaram Padmini, Parasuraman Parimala
Sirtuins have received wide spread attention due to their diverse physiological role in metabolism. Among sirtuins, SIRT2 is more abundant in adipocytes; exerts effect on adipocyte differentiation, a process involves conversion of preadipocytes to mature adipocytes orchestrated by adipokines and adipogenic transcription factors. Grey mullets (Scientific name: Mugil cephalus) were chosen as study organism due to its excellent serve as a biomonitor. Adipocytes isolated from natural field condition were termed as field hypoxic (Ennore) and normoxic (Kovalam) based on DO level in the estuary...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28802040/aged-stem-cells-reprogram-their-daily-rhythmic-functions-to-adapt-to-stress
#8
Guiomar Solanas, Francisca Oliveira Peixoto, Eusebio Perdiguero, Mercè Jardí, Vanessa Ruiz-Bonilla, Debayan Datta, Aikaterini Symeonidi, Andrés Castellanos, Patrick-Simon Welz, Juan Martín Caballero, Paolo Sassone-Corsi, Pura Muñoz-Cánoves, Salvador Aznar Benitah
Normal homeostatic functions of adult stem cells have rhythmic daily oscillations that are believed to become arrhythmic during aging. Unexpectedly, we find that aged mice remain behaviorally circadian and that their epidermal and muscle stem cells retain a robustly rhythmic core circadian machinery. However, the oscillating transcriptome is extensively reprogrammed in aged stem cells, switching from genes involved in homeostasis to those involved in tissue-specific stresses, such as DNA damage or inefficient autophagy...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28802039/circadian-reprogramming-in-the-liver-identifies-metabolic-pathways-of-aging
#9
Shogo Sato, Guiomar Solanas, Francisca Oliveira Peixoto, Leonardo Bee, Aikaterini Symeonidi, Mark S Schmidt, Charles Brenner, Selma Masri, Salvador Aznar Benitah, Paolo Sassone-Corsi
The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and rewires circadian metabolism. Using young versus old mice, fed ad libitum or under CR, we reveal reprogramming of the circadian transcriptome in the liver. These age-dependent changes occur in a highly tissue-specific manner, as demonstrated by comparing circadian gene expression in the liver versus epidermal and skeletal muscle stem cells...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28801668/exercise-leads-to-unfavourable-cardiac-remodelling-and-enhanced-metabolic-homeostasis-in-obese-mice-with-cardiac-and-skeletal-muscle-autophagy-deficiency
#10
Zhen Yan, Ana Kronemberger, Jay Blomme, Jarrod A Call, Hannah M Caster, Renata O Pereira, Henan Zhao, Vitor U de Melo, Rhianna C Laker, Mei Zhang, Vitor A Lira
Autophagy is stimulated by exercise in several tissues; yet the role of skeletal and cardiac muscle-specific autophagy on the benefits of exercise training remains incompletely understood. Here, we determined the metabolic impact of exercise training in obese mice with cardiac and skeletal muscle disruption of the Autophagy related 7 gene (Atg7(h&mKO)). Muscle autophagy deficiency did not affect glucose clearance and exercise capacity in lean adult mice. High-fat diet in sedentary mice led to endoplasmic reticulum stress and aberrant mitochondrial protein expression in autophagy-deficient skeletal and cardiac muscles...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798698/%C3%AE-catenin-knockdown-affects-mitochondrial-biogenesis-and-lipid-metabolism-in-breast-cancer-cells
#11
Daniele Vergara, Eleonora Stanca, Flora Guerra, Paola Priore, Antonio Gaballo, Julien Franck, Pasquale Simeone, Marco Trerotola, Stefania De Domenico, Isabelle Fournier, Cecilia Bucci, Michel Salzet, Anna M Giudetti, Michele Maffia
β-catenin plays an important role as regulatory hub in several cellular processes including cell adhesion, metabolism, and epithelial mesenchymal transition. This is mainly achieved by its dual role as structural component of cadherin-based adherens junctions, and as a key nuclear effector of the Wnt pathway. For this dual role, different classes of proteins are differentially regulated via β-catenin dependent mechanisms. Here, we applied a liquid chromatography-mass spectrometry (LC-MS/MS) approach to identify proteins modulated after β-catenin knockdown in the breast cancer cell line MCF-7...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28798256/metabolic-characterization-and-rna-profiling-reveal-glycolytic-dependence-of-pro-fibrotic-phenotype-of-alveolar-macrophages-in-lung-fibrosis
#12
Na Xie, Huachun Cui, Jing Ge, Sami Banerjee, Sijia Guo, Shubham Dubey, Edward Abraham, Rui-Ming Liu, Gang Liu
Metabolic reprogramming has been intrinsically linked to macrophage activation. Alveolar macrophages are known to play an important role in the pathogenesis of pulmonary fibrosis. However, systematic characterization of expression profile in these cells is still lacking. Furthermore, main metabolic programs and their regulation of cellular phenotype are completely unknown. In this study, we comprehensively analyzed the expression profile and main metabolic programs in alveolar macrophages from mice with or without experimental pulmonary fibrosis...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28798047/mtor-regulates-metabolic-adaptation-of-apcs-in-the-lung-and-controls-the-outcome-of-allergic-inflammation
#13
Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran
Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working in mouse models of inflammation, we found that mTOR-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for DC homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103(+) DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b(+) DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic Th2 to neutrophilic Th17 polarity...
August 10, 2017: Science
https://www.readbyqxmd.com/read/28794439/maternal-low-intensity-physical-exercise-prevents-obesity-in-offspring-rats-exposed-to-early-overnutrition
#14
Tatiane Aparecida Ribeiro, Laize Peron Tófolo, Isabela Peixoto Martins, Audrei Pavanello, Júlio Cezar de Oliveira, Kelly Valério Prates, Rosiane Aparecida Miranda, Claudinéia Conationi da Silva Franco, Rodrigo Mello Gomes, Flávio Andrade Francisco, Vander Silva Alves, Douglas Lopes de Almeida, Veridiana Mota Moreira, Kesia Palma-Rigo, Elaine Vieira, Gabriel Sergio Fabricio, Marcos Ricardo da Silva Rodrigues, Wilson Rinaldi, Ananda Malta, Paulo Cezar de Freitas Mathias
Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#15
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28791350/prl-3-improves-colorectal-cancer-cell-proliferation-and-invasion-through-il-8-mediated-glycolysis-metabolism
#16
Heyang Xu, Yujie Zeng, Lu Liu, Qian Gao, Shaowen Jin, Qiusheng Lan, Wei Lai, Xingxi Luo, Heng Wu, Yongliang Huang, Zhonghua Chu
Phosphatase of regenerating liver-3 (PRL-3) has been found to be overexpressed in liver metastases of colorectal cancer and rarely expressed in primary tumors, which plays an important role in the metastasis of colorectal cancer cells. Metabolism reprogramming has been found to be a hallmark of cancer cells, and aerobic glycolysis is a metabolic adaption for cancer cells and promotes cell proliferation. However, the association between PRL-3 and glycolysis in colorectal cancer cells is not well understood. In the present study, we explored the association between PRL-3 and glycolysis...
August 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28789945/ambra1-is-involved-in-t-cell-receptor-mediated-metabolic-reprogramming-through-an-atg7-independent-pathway
#17
Hisako Akatsuka, Shuhei Kuga, Kaori Masuhara, Odontuya Davaadorj, Chisa Okada, Yumi Iida, Yoshinori Okada, Nahoko Fukunishi, Takahiro Suzuki, Kazuyoshi Hosomichi, Masato Ohtsuka, Masafumi Tanaka, Ituro Inoue, Minoru Kimura, Takehito Sato
Metabolic reprogramming contributes to dynamic alteration of cell functions and characteristics. In T cells, TCR-mediated signaling evokes metabolic reprogramming and autophagy. AMBRA1 is known to serve in the facilitation of autophagy and quality control of mitochondria, but the role of AMBRA1 in T cell metabolic alteration is unknown. Here, we show that AMBRA1, but not ATG7, plays a role in TCR-mediated control of glycolytic factors and mitochondrial mass, while both AMBRA1 and ATG7 are required for autolysosome formation...
August 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28783731/metabolic-control-of-th17-and-induced-treg-cell-balance-by-an-epigenetic-mechanism
#18
Tao Xu, Kelly M Stewart, Xiaohu Wang, Kai Liu, Min Xie, Jae Kyu Ryu, Ke Li, Tianhua Ma, Haixia Wang, Lu Ni, Saiyong Zhu, Nan Cao, Dongwei Zhu, Yu Zhang, Katerina Akassoglou, Chen Dong, Edward M Driggers, Sheng Ding
Metabolism has been shown to integrate with epigenetics and transcription to modulate cell fate and function. Beyond meeting the bioenergetic and biosynthetic demands of T-cell differentiation, whether metabolism might control T-cell fate by an epigenetic mechanism is unclear. Here, through the discovery and mechanistic characterization of a small molecule, (aminooxy)acetic acid, that reprograms the differentiation of T helper 17 (TH17) cells towards induced regulatory T (iTreg) cells, we show that increased transamination, mainly catalysed by GOT1, leads to increased levels of 2-hydroxyglutarate in differentiating TH17 cells...
August 2, 2017: Nature
https://www.readbyqxmd.com/read/28783377/extracellular-mitochondrial-dna-is-generated-by-fibroblasts-and-predicts-death-in-idiopathic-pulmonary-fibrosis
#19
Changwan Ryu, Huanxing Sun, Mridu Gulati, Jose D Herazo-Maya, Yonglin Chen, Awo Osafo-Addo, Caitlin Brandsdorfer, Julia Winkler, Christina Blaul, Jaden Faunce, Hongyi Pan, Tony Woolard, Argyrios Tzouvelekis, Danielle E Antin-Ozerkis, Jonathan T Puchalski, Martin Slade, Anjelica L Gonzalez, Daniel F Bogenhagen, Varvara Kirillov, Carol Feghali-Bostwick, Kevin Gibson, Kathleen Lindell, Raimund I Herzog, Charles S Dela Cruz, Wajahat Mehal, Naftali Kaminski, Erica Herzog, Glenda Trujillo
RATIONALE: Idiopathic pulmonary fibrosis (IPF) involves the accumulation of alpha smooth muscle actin (αSMA) expressing myofibroblasts arising from interactions with soluble mediators such as transforming growth factor beta-1 (TGFβ1), and mechanical influences such as local tissue stiffness. While IPF fibroblasts are enriched for aerobic glycolysis and innate immune receptor activation, innate immune ligands related to mitochondrial injury, such as extracellular mitochondrial DNA (mtDNA) have not been identified in IPF...
August 7, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28781079/rapid-generation-of-human-genetic-loss-of-function-ipsc-lines-by-simultaneous-reprogramming-and-gene-editing
#20
Andrew M Tidball, Louis T Dang, Trevor W Glenn, Emma G Kilbane, Daniel J Klarr, Joshua L Margolis, Michael D Uhler, Jack M Parent
Specifically ablating genes in human induced pluripotent stem cells (iPSCs) allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF) mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels). This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls...
July 24, 2017: Stem Cell Reports
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