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Metabolism and epigenetic

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https://www.readbyqxmd.com/read/28325086/application-of-bacterial-reverse-mutation-assay-for-detection-of-non-genotoxic-carcinogens
#1
Rewan Kanode, Saurabh Chandra, Sharad Sharma
Non-genotoxic carcinogens may play a significant role in development of cancer. Currently short-term assays for mutagenicity classify genotoxic carcinogens and lack the abilities to detect epigenetic carcinogens. The need to develop an endpoint always remains to recognize potentially carcinogenic agents employing rapid and practical bioassays. For this, the present study utilized TA98 and TA1537 tester strains of Salmonella typhimurium to evaluate four non-genotoxic carcinogenic agents (Coumarin, β-Myrcene, Bis(2-ethylhexyl) phthalate and trans-anethole)...
March 22, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28324105/thyroid-hormone-dependent-epigenetic-regulation-of-melanocortin-4-receptor-levels-in-female-offspring-of-obese-rats
#2
T Tabachnik, T Kisliouk, A Marco, N Meiri, A Weller
Maternal obesity is a risk factor for offspring obesity. Melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. This study examines epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in offspring of high-fat diet (HFD)-induced obese dams, and aims to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed HFD or chow from weaning through gestation and lactation...
January 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323978/assisted-reproductive-technologies-predispose-to-insulin-resistance-and-obesity-in-male-mice-challenged-with-a-high-fat-diet
#3
David Cerny, Claudio Sartori, Stefano F Rimoldi, Théo Meister, Rodrigo Soria, Elisa Bouillet, Urs Scherrer, Emrush Rexhaj
ART alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the eNOS gene. In eNOS deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We, therefore, assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high fat diet (HFD) during 8 weeks...
February 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#4
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28321369/developmental-and-loco-like-effects-of-a-swainsonine-induced-inhibition-of-%C3%AE-mannosidase-in-the-honey-bee-apis-mellifera
#5
Laura Wedd, Regan Ashby, Sylvain Foret, Ryszard Maleszka
BACKGROUND: Deficiencies in lysosomal a-mannosidase (LAM) activity in animals, caused either by mutations or by consuming toxic alkaloids, lead to severe phenotypic and behavioural consequences. Yet, epialleles adversely affecting LAM expression exist in the honey bee population suggesting that they might be beneficial in certain contexts and cannot be eliminated by natural selection. METHODS: We have used a combination of enzymology, molecular biology and metabolomics to characterise the catalytic properties of honey bee LAM (AmLAM) and then used an indolizidine alkaloid swainsonine to inhibit its activity in vitro and in vivo...
2017: PeerJ
https://www.readbyqxmd.com/read/28320830/exercise-and-the-skeletal-muscle-epigenome
#6
Sean L McGee, Ken R Walder
An acute bout of exercise is sufficient to induce changes in skeletal muscle gene expression that are ultimately responsible for the adaptive responses to exercise. Although much research has described the intracellular signaling responses to exercise that are linked to transcriptional regulation, the epigenetic mechanisms involved are only just emerging. This review will provide an overview of epigenetic mechanisms and what is known in the context of exercise. Additionally, we will explore potential interactions between metabolism during exercise and epigenetic regulation, which serves as a framework for potential areas for future research...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28320484/nutritional-intervention-preconception-and-during-pregnancy-to-maintain-healthy-glucose-metabolism-and-offspring-health-nipper-study-protocol-for-a-randomised-controlled-trial
#7
Keith M Godfrey, Wayne Cutfield, Shiao-Yng Chan, Philip N Baker, Yap-Seng Chong
BACKGROUND: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health...
March 20, 2017: Trials
https://www.readbyqxmd.com/read/28315358/isocitrate-dehydrogenase-idh-inhibition-as-treatment-of-myeloid-malignancies-progress-and-future-directions
#8
REVIEW
Vivek A Upadhyay, Andrew M Brunner, Amir T Fathi
Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme. Over the last two decades, there has been a growing focus on the metabolic derangements that occur with IDH1 and IDH2 mutations. The altered IDH protein leads to accumulation of 2-hydroxyglutarate (2-HG), a metabolite with oncogenic activity via epigenetic mechanisms. The advent of IDH inhibitors has engendered hope in novel and targeted therapies in IDH1/2 mutant myeloid malignancies. We here summarize the basic physiology of IDH, the metabolic and oncogenic consequences of mutant IDH1/2, and the clinical significance of IDH inhibition in hematologic malignancies...
March 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#9
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#10
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28314754/kdm6b-regulates-cartilage-development-and-homeostasis-through-anabolic-metabolism
#11
Jun Dai, Dongsheng Yu, Yafei Wang, Yishan Chen, Heng Sun, Xiaolei Zhang, Shouan Zhu, Zongyou Pan, Boon Chin Heng, Shufang Zhang, Hongwei Ouyang
OBJECTIVES: Epigenetic mechanisms have been reported to play key roles in chondrogenesis and osteoarthritis (OA) development. Here, we sought to identify specific histone demethylases that are involved and delineate the underlying mechanisms. METHODS: We screened the expression of 17 distinct histone demethylases by quantitative real time PCR (qRT-PCR) during chondrogenic differentiation of C3H10T1/2 cells. The role of Kdm6b in cartilage development was then analysed with transgenic Col2a1-CreER(T2);Kdm6b(f/f) ...
March 17, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28302867/an-early-life-hypoxia-event-has-a-long-term-impact-on-protein-digestion-and-growth-in-european-sea-bass-juvenile
#12
José L Zambonino-Infante, David Mazurais, A Servili, C Cahu, G Vanderplancke, N Le Bayon, C Huelvan, Guy Claireaux
Ocean warming, eutrophication and consequent decrease in oxygen lead to smaller average fish size. Although such responses are well-known in an evolutionary context, involving multiple generations, it appears to be incompatible with current rapid environmental change. Rather, phenotypic plasticity could provide a means for marine fish to cope with rapid environmental changes. However, little is known about the mechanisms underlying plastic responses to environmental conditions that favour small phenotypes.Our aim was to investigate how and why European sea bass that had experienced a short episode of moderate hypoxia during their larval stage subsequently exhibited a growth depression at the juvenile stage compared to the control group...
March 16, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28301983/applying-systems-biology-methodology-to-identify-genetic-factors-possibly-associated-with-recovery-after-traumatic-brain-injury
#13
Brad G Kurowski, Amery Treble-Barna, Alexis J Pitzer, Shari L Wade, Lisa J Martin, Ranjit S Chima, Anil Jegga
Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality worldwide. It is linked with a number of medical, neurological, cognitive, and behavioral sequelae. The influence of genetic factors on the biology and related recovery after TBI is poorly understood. Studies that seek to elucidate the impact of genetic influences on neurorecovery after TBI will lead to better individualization of prognosis and inform development of novel treatments, which are considerably lacking. Current genetic studies related to TBI have focused on specific candidate genes...
March 16, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28298479/cyst-nematode-parasitism-induces-dynamic-changes-in-the-root-epigenome
#14
Tarek Hewezi, Thomas Lane, Sarbottam Piya, Aditi Rambani, J Hollis Rice, Meg Staton
A growing body of evidence indicates that epigenetic modifications can provide efficient, dynamic, and reversible cellular responses to a wide range of environmental stimuli. However, the significance of epigenetic modifications in plant-pathogen interactions remains largely unexplored. In this study, we provide a comprehensive analysis of epigenome changes during the compatible interaction between the beet cyst nematode Heterodera schachtii and Arabidopsis (Arabidopsis thaliana). Whole genome bisulfite sequencing was conducted to assess the dynamic changes in the methylome of Arabidopsis roots in response to H schachtii infection...
March 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28296592/ethanol-extract-of-capsella-bursa-pastoris-improves-hepatic-steatosis-through-inhibition-of-histone-acetyltransferase-activity
#15
Hyo-Kyoung Choi, Eun Ju Shin, Su Jin Park, Haeng Jeon Hur, Jae Ho Park, Min-Yu Chung, Myung Sunny Kim, Jin-Taek Hwang
Histone lysine acetylation is thought to play a role in regulating the balance between energy storage and energy expenditure. However, the epigenetic mechanisms by which food phytochemicals influence metabolic processes in the liver have not been thoroughly investigated. In this study, we investigated the effect of an ethanol extract of Capsella bursa-pastoris (ECB) on histone acetyltransferase (HAT) inhibition, and whether it could thereby attenuate lipid accumulation in vitro and in vivo. We observed that ECB inhibits HAT activity as assessed by colorimetric and autoradiography assay systems...
March 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28291256/exercise-rescues-obese-mothers-insulin-sensitivity-placental-hypoxia-and-male-offspring-insulin-sensitivity
#16
Denise S Fernandez-Twinn, Geraldine Gascoin, Barbara Musial, Sarah Carr, Daniella Duque-Guimaraes, Heather L Blackmore, Maria Z Alfaradhi, Elena Loche, Amanda N Sferruzzi-Perri, Abigail L Fowden, Susan E Ozanne
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290496/transcriptome-analysis-of-a-wild-bird-reveals-physiological-responses-to-the-urban-environment
#17
Hannah Watson, Elin Videvall, Martin N Andersson, Caroline Isaksson
Identifying the molecular basis of environmentally induced phenotypic variation presents exciting opportunities for furthering our understanding of how ecological processes and the environment can shape the phenotype. Urban and rural environments present free-living organisms with different challenges and opportunities, which have marked consequences for the phenotype, yet little is known about responses at the molecular level. We characterised transcriptomes from an urban and a rural population of great tits Parus major, demonstrating striking differences in gene expression profiles in both blood and liver tissues...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289216/b-vitamins-attenuate-the-epigenetic-effects-of-ambient-fine-particles-in-a-pilot-human-intervention-trial
#18
Jia Zhong, Oskar Karlsson, Guan Wang, Jun Li, Yichen Guo, Xinyi Lin, Michele Zemplenyi, Marco Sanchez-Guerra, Letizia Trevisi, Bruce Urch, Mary Speck, Liming Liang, Brent A Coull, Petros Koutrakis, Frances Silverman, Diane R Gold, Tangchun Wu, Andrea A Baccarelli
Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28289190/ampk-blocks-starvation-inducible-transgenerational-defects-in-caenorhabditis-elegans
#19
Emilie Demoinet, Shaolin Li, Richard Roy
Life history events, such as traumatic stress, illness, or starvation, can influence us through molecular changes that are recorded in a pattern of characteristic chromatin modifications. These modifications are often associated with adaptive adjustments in gene expression that can persist throughout the lifetime of the organism, or even span multiple generations. Although these adaptations may confer some selective advantage, if they are not appropriately regulated they can also be maladaptive in a context-dependent manner...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28283292/mixture-specific-gene-expression-in-zebrafish-danio-rerio-embryos-exposed-to-perfluorooctane-sulfonic-acid-pfos-perfluorohexanoic-acid-pfhxa-and-3-3-4-4-5-pentachlorobiphenyl-pcb126
#20
Mélanie Blanc, Anna Kärrman, Petr Kukucka, Nikolai Scherbak, Steffen Keiter
Perfluorooctane sulfonic acid (PFOS) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are persistent organic pollutants of high concern because of their environmental persistence, bioaccumulation and toxic properties. Besides, the amphiphilic properties of fluorinated compounds such as PFOS and perfluorohexanoic acid (PFHxA) suggest a role in increasing cell membrane permeability and solubilizing chemicals. The present study aimed at investigating whether PFOS and PFHxA are capable of modifying the activation of PCB126 toxicity-related pathways...
March 7, 2017: Science of the Total Environment
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