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Metabolism and epigenetic

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https://www.readbyqxmd.com/read/29675460/epigenetic-reprogramming-of-human-hepatoma-cells-a-low-cost-option-for-drug-metabolism-assessment
#1
Luc Gailhouste, Lee Chuen Liew, Ken Yasukawa, Keitaro Hagiwara, Norihiko Iwazaki, Yasuhiro Yamada, Izuho Hatada, Takahiro Ochiya
No abstract text is available yet for this article.
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29674714/mechanisms-of-physiological-and-pathological-cardiac-hypertrophy
#2
REVIEW
Michinari Nakamura, Junichi Sadoshima
Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure...
April 19, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29674394/acetyl-coa-promotes-glioblastoma-cell-adhesion-and-migration-through-ca-2-nfat-signaling
#3
Joyce V Lee, Corbett T Berry, Karla Kim, Payel Sen, Taehyong Kim, Alessandro Carrer, Sophie Trefely, Steven Zhao, Sully Fernandez, Lauren E Barney, Alyssa D Schwartz, Shelly R Peyton, Nathaniel W Snyder, Shelley L Berger, Bruce D Freedman, Kathryn E Wellen
The metabolite acetyl-coenzyme A (acetyl-CoA) is the required acetyl donor for lysine acetylation and thereby links metabolism, signaling, and epigenetics. Nutrient availability alters acetyl-CoA levels in cancer cells, correlating with changes in global histone acetylation and gene expression. However, the specific molecular mechanisms through which acetyl-CoA production impacts gene expression and its functional roles in promoting malignant phenotypes are poorly understood. Here, using histone H3 Lys27 acetylation (H3K27ac) ChIP-seq (chromatin immunoprecipitation [ChIP] coupled with next-generation sequencing) with normalization to an exogenous reference genome (ChIP-Rx), we found that changes in acetyl-CoA abundance trigger site-specific regulation of H3K27ac, correlating with gene expression as opposed to uniformly modulating this mark at all genes...
April 19, 2018: Genes & Development
https://www.readbyqxmd.com/read/29673926/the-investigations-of-genetic-determinants-of-the-metabolic-syndrome
#4
REVIEW
Behdokht Fathi Dizaji
Metabolic syndrome is the aggregation of cardiovascular risk factors that increases the risk of type 2 diabetes and cardiovascular diseases. Family and twin studies, heritability spectrum for its components and different prevalence among ethnicities, have provided genetic susceptibility to the metabolic syndrome. The investigations of genetic base for the disorder have recognized numerous chromosomes, various DNA polymorphisms in candidate genes and many gene variants, that are associated with metabolic syndrome as an entity or its traits, which mostly are related to lipid metabolism...
April 11, 2018: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/29673874/origins-of-lifetime-health-around-the-time-of-conception-causes-and-consequences
#5
REVIEW
Tom P Fleming, Adam J Watkins, Miguel A Velazquez, John C Mathers, Andrew M Prentice, Judith Stephenson, Mary Barker, Richard Saffery, Chittaranjan S Yajnik, Judith J Eckert, Mark A Hanson, Terrence Forrester, Peter D Gluckman, Keith M Godfrey
Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming...
April 16, 2018: Lancet
https://www.readbyqxmd.com/read/29672864/menin-regulates-the-serine-biosynthetic-pathway-in-ewing-sarcoma
#6
Laurie K Svoboda, Selina Shiqing K Teh, Sudha Sud, Samuel Kerk, Aaron Zebolsky, Sydney Treichel, Dafydd Thomas, Christopher J Halbrook, Ho-Joon Lee, Daniel Kremer, Li Zhang, Szymon Klossowski, Armand R Bankhead, Brian Magnuson, Mats Ljungman, Tomasz Cierpicki, Jolanta Grembecka, Costas A Lyssiotis, Elizabeth R Lawlor
Developmental transcription programs are epigenetically regulated by multi-protein complexes, including the menin- and MLL-containing trithorax (TrxG) complexes, which promote gene transcription by depositing the H3K4me3 activating mark at target gene promoters. We recently reported that in Ewing sarcoma, MLL1 (lysine methyltransferase 2A, KMT2A) and menin are overexpressed and function as oncogenes. Small molecule inhibition of the menin-MLL interaction leads to loss of menin and MLL1 protein expression and to inhibition of growth and tumorigenicity...
April 19, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29671161/under-evaluated-or-unassessed-pathogenic-pathways-in-autoimmune-hepatitis-and-implications-for-future-management
#7
REVIEW
Albert J Czaja
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells...
April 18, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29670690/discovery-of-ag-120-ivosidenib-a-first-in-class-mutant-idh1-inhibitor-for-the-treatment-of-idh1-mutant-cancers
#8
Janeta Popovici-Muller, René M Lemieux, Erin Artin, Jeffrey O Saunders, Francesco G Salituro, Jeremy Travins, Giovanni Cianchetta, Zhenwei Cai, Ding Zhou, Dawei Cui, Ping Chen, Kimberly Straley, Erica Tobin, Fang Wang, Muriel D David, Virginie Penard-Lacronique, Cyril Quivoron, Véronique Saada, Stéphane de Botton, Stefan Gross, Lenny Dang, Hua Yang, Luke Utley, Yue Chen, Hyeryun Kim, Shengfang Jin, Zhiwei Gu, Gui Yao, Zhiyong Luo, Xiaobing Lv, Cheng Fang, Liping Yan, Andrew Olaharski, Lee Silverman, Scott Biller, Shin-San M Su, Katharine Yen
Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors. Here, we report the discovery of AG-120 (ivosidenib), an inhibitor of the IDH1 mutant enzyme that exhibits profound 2-HG lowering in tumor models and the ability to effect differentiation of primary patient AML samples ex vivo...
April 12, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29670212/mitochondrial-dna-variation-and-the-pathogenesis-of-osteoarthritis-phenotypes
#9
REVIEW
Francisco J Blanco, Ana M Valdes, Ignacio Rego-Pérez
Mitochondria and mitochondrial DNA (mtDNA) variation are now recognized as important factors in the development of osteoarthritis (OA). Mitochondria are the energy powerhouses of the cell, and also regulate different processes involved in the pathogenesis of OA including inflammation, apoptosis, calcium metabolism and the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Mitochondria contain their own genetic material, mtDNA, which evolved through the sequential accumulation of mtDNA variants to enable humans to adapt to different climates...
April 18, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29669855/squalene-epoxidase-drives-nafld-induced-hepatocellular-carcinoma-and-is-a-pharmaceutical-target
#10
Dabin Liu, Chi Chun Wong, Li Fu, Huarong Chen, Liuyang Zhao, Chuangen Li, Yunfei Zhou, Yanquan Zhang, Weiqi Xu, Yidong Yang, Bin Wu, Gong Cheng, Paul Bo-San Lai, Nathalie Wong, Joseph J Y Sung, Jun Yu
Nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world; however, mechanisms that contribute to its formation are largely unknown, and targeted therapy is currently not available. Our RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase ( SQLE ) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Hepatocyte-specific Sqle transgenic expression in mice accelerated the development of high-fat, high-cholesterol diet-induced HCC...
April 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29668680/mitochondrial-nicotinamide-adenine-dinucleotide-reduced-nadh-oxidation-links-the-tricarboxylic-acid-tca-cycle-with-methionine-metabolism-and-nuclear-dna-methylation
#11
Oswaldo A Lozoya, Inmaculada Martinez-Reyes, Tianyuan Wang, Dagoberto Grenet, Pierre Bushel, Jianying Li, Navdeep Chandel, Richard P Woychik, Janine H Santos
Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle...
April 18, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29666451/exploring-the-extent-and-scope-of-epigenetic-inheritance
#12
REVIEW
Elizabeth J Radford
Environmental factors, particularly during early life, are important for the later metabolic health of the individual. In our obesogenic environment, it is of major socio-economic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Increasing evidence from a variety of model organisms suggests that non-genetically determined phenotypes, including metabolic effects such as glucose intolerance and obesity, can be passed between generations, which encourages us to revisit heredity...
April 17, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29666172/genetic-editing-of-colonic-organoids-provides-a-molecularly-distinct-and-orthotopic-preclinical-model-of-serrated-carcinogenesis
#13
Tamsin R M Lannagan, Young K Lee, Tongtong Wang, Jatin Roper, Mark L Bettington, Lochlan Fennell, Laura Vrbanac, Lisa Jonavicius, Roshini Somashekar, Krystyna Gieniec, Miao Yang, Jia Q Ng, Nobumi Suzuki, Mari Ichinose, Josephine A Wright, Hiroki Kobayashi, Tracey L Putoczki, Yoku Hayakawa, Simon J Leedham, Helen E Abud, Ömer H Yilmaz, Julie Marker, Sonja Klebe, Pratyaksha Wirapati, Siddhartha Mukherjee, Sabine Tejpar, Barbara A Leggett, Vicki L J Whitehall, Daniel L Worthley, Susan L Woods
OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF , and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein...
April 17, 2018: Gut
https://www.readbyqxmd.com/read/29665673/cooperative-instruction-of-signaling-and-metabolic-pathways-on-the-epigenetic-landscape
#14
Jung-Ae Kim
Cells cope with diverse intrinsic and extrinsic stimuli in order to make adaptations for survival. The epigenetic landscape plays a crucial role in cellular adaptation, as it integrates the information generated from stimuli. Signaling pathways induced by stimuli communicate with chromatin to change the epigenetic landscape through regulation of epigenetic modifiers. Metabolic dynamics altered by these stimuli also affect the activity of epigenetic modifiers. Here, I review the current understanding of epigenetic regulation via signaling and metabolic pathways...
April 11, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29663393/maternal-obesity-reprograms-offspring-s-executive-brain-centers-in-a-sex-specific-manner-an-editorial-for-perinatal-high-fat-diet-and-early-life-methyl-donor-supplementation-alter-one-carbon-metabolism-and-dna-methylation-in-the-brain-on-doi-10-1111-jnc-14319
#15
EDITORIAL
Kaja Plucińska, Steven W Barger
This editorial highlights an article by McKee and colleagues in the current issue of Journal of Neurochemistry, in which the authors report epigenetic changes linked to one-carbon metabolism in prefrontal cortex (PFC) of murine offspring from dams fed high-fat diet to mimic maternal obesity. The group found that high-fat diet feeding in utero increases weight gain in offspring and dynamically alters DNA methylation in the PFC of male but not female brains. These epigenetic marks were associated with a shift in brain one-carbon metabolism (folate and methionine) intermediates and were normalized by early-life methyl-donor supplementation in a sex-specific manner...
April 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29662077/pharmacodynamics-of-mutant-idh1-inhibitors-in-glioma-patients-probed-by-in-vivo-3d-mrs-imaging-of-2-hydroxyglutarate
#16
Ovidiu C Andronesi, Isabel C Arrillaga-Romany, K Ina Ly, Wolfgang Bogner, Eva M Ratai, Kara Reitz, A John Iafrate, Jorg Dietrich, Elizabeth R Gerstner, Andrew S Chi, Bruce R Rosen, Patrick Y Wen, Daniel P Cahill, Tracy T Batchelor
Inhibitors of the mutant isocitrate dehydrogenase 1 (IDH1) entered recently in clinical trials for glioma treatment. Mutant IDH1 produces high levels of 2-hydroxyglurate (2HG), thought to initiate oncogenesis through epigenetic modifications of gene expression. In this study, we show the initial evidence of the pharmacodynamics of a new mutant IDH1 inhibitor in glioma patients, using non-invasive 3D MR spectroscopic imaging of 2HG. Our results from a Phase 1 clinical trial indicate a rapid decrease of 2HG levels by 70% (CI 13%, P = 0...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29661859/mitochondria-and-the-dynamic-control-of-stem-cell-homeostasis
#17
REVIEW
Pawel Lisowski, Preethi Kannan, Barbara Mlody, Alessandro Prigione
The maintenance of cellular identity requires continuous adaptation to environmental changes. This process is particularly critical for stem cells, which need to preserve their differentiation potential over time. Among the mechanisms responsible for regulating cellular homeostatic responses, mitochondria are emerging as key players. Given their dynamic and multifaceted role in energy metabolism, redox, and calcium balance, as well as cell death, mitochondria appear at the interface between environmental cues and the control of epigenetic identity...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29661250/isocitrate-dehydrogenase-1-snail-axis-dysfunction-significantly-correlates-with-breast-cancer-prognosis-and-regulates-cell-invasion-ability
#18
Wen-Shan Liu, Shih-Hsuan Chan, Hong-Tai Chang, Guan-Cheng Li, Ya-Ting Tu, Hui-Hwa Tseng, Ting-Ying Fu, Hui-Yu Chang, Huei-Han Liou, Luo-Ping Ger, Kuo-Wang Tsai
BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma...
April 16, 2018: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29657328/non-canonical-functions-of-enzymes-facilitate-cross-talk-between-cell-metabolic-and-regulatory-pathways
#19
REVIEW
Marteinn T Snaebjornsson, Almut Schulze
The metabolic rewiring that occurs during cell transformation is a hallmark of cancer. It is diverse in different cancers as it reflects different combinations of oncogenic drivers, tumor suppressors, and the microenvironment. Metabolic rewiring is essential to cancer as it enables uncontrolled proliferation and adaptation to the fluctuating availability of nutrients and oxygen caused by poor access to the vasculature due to tumor growth and a foreign microenvironment encountered during metastasis. Increasing evidence now indicates that the metabolic state in cancer cells also plays a causal role in tumor growth and metastasis, for example through the action of oncometabolites, which modulate cell signaling and epigenetic pathways to promote malignancy...
April 16, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29645315/cell-and-molecular-mechanisms-behind-diet-induced-hypothalamic-inflammation-and-obesity
#20
REVIEW
Yenniffer Ávalos, Bredford Kerr, Manuel Maliqueo, Mauricio Dorfman
Diet-induced obesity (DIO) is associated with chronic, low-grade inflammation in the hypothalamus, a key regulator of energy homeostasis. Current studies have revealed the involvement of different cell types as well as cell and molecular mechanisms that contribute to diet-induced hypothalamic inflammation (DIHI) and DIO. Since the discovery that high-fat diet and saturated fatty acids (SFAs) increase the expression of hypothalamic cytokines prior to weight gain, research has focused on understanding the cellular and molecular mechanisms underlying these changes, and what the role of inflammation in the obesity pathogenesis...
April 12, 2018: Journal of Neuroendocrinology
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