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Metabolism and epigenetic

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https://www.readbyqxmd.com/read/29035547/pharmacokinetics-and-pharmacodynamics-of-the-triterpenoid-ursolic-acid-in-regulating-the-anti-oxidant-anti-inflammatory-and-epigenetic-gene-responses-in-rat-leukocytes
#1
Chengyue Zhang, Chao Wang, Wenji Li, Renyi Wu, Yue Guo, David Cheng, Yuqing Yang, Ioannis P Androulakis, Ah-Ng Kong
The triterpenoid ursolic acid (UA) has been proposed as a potential cancer chemopreventive agent in many preclinical and clinical studies. In the present work, we aimed to characterize the pharmacokinetics (PK) of UA and to quantitatively assess the anti-oxidative and anti-inflammatory effects of UA, which are potentially linked to its chemopreventive efficacy. UA was administered intravenously (i.v., 20 mg/kg) or by oral gavage (100 mg/kg) to male Sprague-Dawley rats, and blood samples were collected at a series of designated time points...
October 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29033534/multicellular-tumor-spheroids-of-human-uveal-melanoma-induce-genes-associated-with-anoikis-resistance-lipogenesis-and-ssxs
#2
Charlotte Ness, Øystein Garred, Nils A Eide, Theresa Kumar, Ole K Olstad, Thomas P Bærland, Goran Petrovski, Morten C Moe, Agate Noer
PURPOSE: Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40-50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistance, and an adaptive cellular metabolism. The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by anchorage-independent growth enriches for a more aggressive phenotype...
2017: Molecular Vision
https://www.readbyqxmd.com/read/29032385/exercise-training-response-heterogeneity-physiological-and-molecular-insights
#3
REVIEW
Lauren M Sparks
The overall beneficial effects of exercise are well studied, but why some people do not respond favourably to exercise is less understood. The National Institutes of Health Common Fund has recently launched the large-scale discovery project 'Molecular Transducers of Physical Activity in Humans' to examine the physiological and molecular (i.e. genetic, epigenetic, lipidomic, metabolomic, proteomic, etc.) responses to exercise training. A nationwide, multicentre clinical trial such as this one also provides a unique opportunity to robustly investigate the non-response to exercise in thousands of individuals that have undergone supervised aerobic- and resistance-based exercise training interventions...
October 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/29031714/dwarfism-and-insulin-resistance-in-male-offspring-caused-by-%C3%AE-1-adrenergic-antagonism-during-pregnancy
#4
Rebecca Oelkrug, Beate Herrmann, Cathleen Geissler, Lisbeth Harder, Christiane Koch, Hendrik Lehnert, Henrik Oster, Henriette Kirchner, Jens Mittag
OBJECTIVE: Maternal and environmental factors control the epigenetic fetal programming of the embryo, thereby defining the susceptibility for metabolic or endocrine disorders in the offspring. Pharmacological interventions required as a consequence of gestational problems, e.g. hypertension, can potentially interfere with correct fetal programming. As epigenetic alterations are usually only revealed later in life and not detected in studies focusing on early perinatal outcomes, little is known about the long-term epigenetic effects of gestational drug treatments...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030989/genetic-and-epigenetic-factors-influencing-vitamin-d-status
#5
REVIEW
Afsane Bahrami, Hamid Reza Sadeghnia, Seyed-Amir Tabatabaeizadeh, Hamidreza Bahrami-Taghanaki, Negin Behboodi, Habibollah Esmaeili, Gordon A Ferns, Majid Ghayour Mobarhan, Amir Avan
The global prevalence of vitamin D deficiency appears to be increasing, and the impact of this on human health is important because of the association of vitamin D insufficiency with increased risk of osteoporosis, cardiovascular disease and some cancers. There are few studies on the genetic factors that can influence vitamin D levels. In particular, the data from twin and family-based studies have reported that circulating vitamin D concentrations are partially determined by genetic factors. Moreover, it has been shown that genetic variants (e...
October 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29029387/the-%C3%AE-nad-salvage-pathway-and-pkc-mediated-signaling-influence-localized-parp-1-activity-and-ctcf-poly-adp-ribosylation
#6
David J P Henderson, Jj L Miranda, Beverly M Emerson
Poly(ADP)ribosylation (PARylation) of the chromatin architectural protein CTCF is critical for CTCF-dependent regulation of chromatin boundary and insulator elements. Loss of CTCF PARylation results in epigenetic silencing of certain tumor suppressor genes through destabilization of nearby chromatin boundaries. We investigated the metabolic and mechanistic processes that regulate PARP-1-mediated CTCF PARylation in human cancer cell lines and discovered a key role for the expression and activity of β-NAD+ salvage enzymes, NAMPT and NMNAT-1...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29027833/trichostatin-a-and-5-aza-2-deoxycytidine-influence-the-expression-of-cold-induced-genes-in-arabidopsis
#7
Yuan Song, Lijun Liu, Gaopeng Li, Lizhe An, Lining Tian
The expression of cold-induced genes is critical for plants to survive under freezing stress. However, the underlying mechanisms for the decision of when, where, and which genes to express are unclear when a plant meets a sudden temperature drop. Previous studies have demonstrated epigenetics to play a central role in the regulation of gene expression in plant responses to environmental stress. DNA methylation and histone deacetylation are the two most important epigenetic modifications. This study was conducted to investigate the effects of inhibiting DNA methylation and histone deacetylation on gene expression, and to explore the potential role of epigenetics in plant responses to cold stress...
October 13, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29027220/metabolic-regulation-of-macrophage-phenotype-and-function
#8
REVIEW
Shilpi Saha, Irina N Shalova, Subhra K Biswas
Studies in the last 20 years have given us a remarkable insight into the functional and phenotypic diversity of macrophages which reflects their integral role in host defence, homeostasis and pathogenesis. Mouse genetics, transcriptomic and epigenetic studies have provided an ontogenic and molecular perspective to the phenotypic diversity of these cells. Recently, metabolic studies have revealed the crucial role of metabolism and metabolites in shaping the phenotype and function of macrophages. Evidence pertaining to this aspect will be reviewed here...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29025858/histone-modifications-regulate-the-developmental-expression-of-human-hepatic-ugt1a1
#9
Ya-Li Nie, Xiang-Guang Meng, Jing-Yang Liu, Liang Yan, Pei Wang, Hong-Zheng Bi, Quan-Cheng Kan, Li-Rong Zhang
Human UDP-glucuronosyltransferase 1A1 (UGT1A1) is a unique enzyme involved in bilirubin conjugation. We previously characterized the hepatic expression of transcription factors affecting UGT1A1 expression during development. Accordingly, in this study, we characterized the ontogenetic expression of hepatic UGT1A1 from the perspective of epigenetic regulation. We observed significant histone-3-lysine-4 dimethylation (H3K4me2) enrichment in the adult liver and histone-3-lysine-27 trimethylation (H3K27me3) enrichment in the fetal liver, indicating that dynamic alterations of histone methylation were associated with ontogenetic UGT1A1 expression...
October 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29021748/binge-like-sucrose-self-administration-experience-inhibits-cocaine-and-sucrose-seeking-behavior-in-offspring
#10
Qiumin Le, Yanqing Li, Weiqing Hou, Biao Yan, Xiangchen Yu, Haikun Song, Feifei Wang, Lan Ma
Recent studies show that emotional and environmental stimuli promote epigenetic inheritance and influence behavioral development in the subsequent generations. Caloric mal- and under-nutrition has been shown to cause metabolic disturbances in the subsequent generation, but the incentive properties of paternal binge-like eating in offspring is still unknown. Here we show that paternal sucrose self-administration experience could induce inter-generational decrease in both sucrose and cocaine-seeking behavior, and sucrose responding in F1 rats, but not F2, correlated with the performance of F0 rats in sucrose self-administration...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29021282/methionine-metabolism-is-essential-for-sirt1-regulated-mouse-embryonic-stem-cell-maintenance-and-embryonic-development
#11
Shuang Tang, Yi Fang, Gang Huang, Xiaojiang Xu, Elizabeth Padilla-Banks, Wei Fan, Qing Xu, Sydney M Sanderson, Julie F Foley, Scotty Dowdy, Michael W McBurney, David C Fargo, Carmen J Williams, Jason W Locasale, Ziqiang Guan, Xiaoling Li
Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, is critically involved in modulating methionine metabolism, thereby impacting maintenance of mouse embryonic stem cells (mESCs) and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are hypersensitive to methionine restriction/depletion-induced differentiation and apoptosis, primarily due to a reduced conversion of methionine to S-adenosylmethionine...
October 11, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29021174/nutritional-geometry-of-paternal-effects-on-embryo-mortality
#12
Michal Polak, Leigh W Simmons, Joshua B Benoit, Kari Ruohonen, Stephen J Simpson, Samantha M Solon-Biet
Well-established causal links exist between maternal nutritional deficits and embryo health and viability. By contrast, environmental effects operating through the father that could influence embryo mortality have seldom been examined. Yet, ejaculates can require non-trivial resource allocation, and seminal plasma components are increasingly recognized to exert wide-ranging effects on females and offspring, so paternal dietary effects on the embryo should be expected. We test for effects of varying levels of protein (P), carbohydrate (C) and caloric load in adult male diet on embryo mortality in Drosophila melanogaster We demonstrate that macronutrient balance and caloric restriction exert significant effects, and that nutritional effects are more impactful when a prior mating has occurred...
October 11, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29020412/emerging-role-of-one-carbon-metabolism-and-dna-methylation-enrichment-on-%C3%AE-containing-gabaa-receptor-expression-in-the-cerebellum-of-subjects-with-alcohol-use-disorders-aud
#13
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
August 19, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29018509/circrna_0046367-prevents-hepatoxicity-of-lipid-peroxidation-an-inhibitory-role-against-hepatic-steatosis
#14
Xing-Ya Guo, Jian-Neng Chen, Fang Sun, Yu-Qin Wang, Qin Pan, Jian-Gao Fan
Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29018149/hypothesis-stimulation-of-trained-immunity-as-adjunctive-immunotherapy-in-cancer
#15
REVIEW
Mihai G Netea, Leo A B Joosten, Jos W M van der Meer
Cancer immunotherapy has steadily progressed during the past decades, with checkpoint inhibitor therapy becoming the latest and one of the most promising treatments. Despite the progress, most of the patients do not respond or develop resistance, and novel additional approaches are needed to improve the clinical effectiveness of immunotherapy. Trained immunity (TI) has been described recently as a process of epigenetic and metabolic reprogramming that induces a long-term enhanced function of innate immune cells...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29018059/involvement-of-leptin-in-the-molecular-physiology-of-the-placenta
#16
Malena Schanton, Julieta Lorena Maymó, Antonio Pérez-Pérez, Victor Sanchez-Margalet, Cecilia Varone
Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenic maternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53 master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placental stimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia, and many other growth hormones, suggesting that it might have an important endocrine function in the trophoblastic cells...
October 9, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28992279/targeting-new-cellular-disease-pathways-in-autosomal-dominant-polycystic-kidney-disease
#17
Ming-Yang Chang, Albert C M Ong
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage renal failure. Understanding the molecular and cellular pathogenesis of ADPKD could help to identify new targets for treatment. The classic cellular cystic phenotype includes changes in proliferation, apoptosis, fluid secretion, extracellular matrix and cilia function. Hoever, recent research, suggests that the cellular cystic phenotype could be broader and that changes, such as altered metabolism, autophagy, inflammation, oxidative stress and epigenetic modification, could play important roles in the processes of cyst initiation, cyst growth or disease progression...
August 29, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#18
K A Gelato, L Schöckel, O Klingbeil, T Rückert, R Lesche, J Toedling, E Kalfon, M Héroult, P Lejeune, U Mönning, A E Fernández-Montalván, S Bäurle, S Siegel, B Haendler
Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28990796/homocysteine-levels-associate-with-subtle-changes-in-leukocyte-dna-methylation-an-epigenome-wide-analysis
#19
Pooja R Mandaviya, Dylan Aïssi, Koen F Dekkers, Roby Joehanes, Silva Kasela, Vinh Truong, Lisette Stolk, Diana van Heemst, M Arfan Ikram, Jan Lindemans, P Eline Slagboom, David-Alexandre Trégouët, André G Uitterlinden, Chen Wei, Phil Wells, France Gagnon, Marleen Mj van Greevenbroek, Bastiaan T Heijmans, Lili Milani, Pierre-Emmanuel Morange, Joyce Bj van Meurs, Sandra G Heil
AIM: Homocysteine (Hcy) is a sensitive marker of one-carbon metabolism. Higher Hcy levels have been associated with global DNA hypomethylation. We investigated the association between plasma Hcy and epigenome-wide DNA methylation in leukocytes. METHODS: Methylation was measured using Illumina 450 k arrays in 2035 individuals from six cohorts. Hcy-associated differentially methylated positions and regions were identified using meta-analysis. RESULTS: Three differentially methylated positions cg21607669 (SLC27A1), cg26382848 (AJUBA) and cg10701000 (KCNMA1) at chromosome 19, 14 and 10, respectively, were significantly associated with Hcy...
October 9, 2017: Epigenomics
https://www.readbyqxmd.com/read/28990735/metabolism-in-cancer-metastasis-bioenergetics-biosynthesis-and-beyond
#20
REVIEW
Shao Thing Teoh, Sophia Y Lunt
Metabolic changes accompany tumor progression and metastatic dissemination of cancer cells. Yet, until recently, metabolism has received little attention in the study of cancer metastasis. Cancer cells undergo significant metabolic rewiring as they acquire metastatic traits and adapt to survive in multiple environments with varying nutrient availability, oxygen concentrations, and extracellular signals. Therefore, to effectively treat metastatic cancer, it is important to understand the metabolic strategies adopted by cancer cells during the metastatic process...
October 9, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
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