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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#1
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#2
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28629775/8-oxo-7-8-dihydroguanine-friend-and-foe-epigenetic-like-regulator-versus-initiator-of-mutagenesis
#3
REVIEW
Aaron M Fleming, Cynthia J Burrows
A high flux of reactive oxygen species during oxidative stress results in oxidative modification of cellular components including DNA. Oxidative DNA "damage" to the heterocyclic bases is considered deleterious because polymerases may incorrectly read the modifications causing mutations. A prominent member in this class is the oxidized guanine base 8-oxo-7,8-dihydroguanine (OG) that is moderately mutagenic effecting G→T transversion mutations. Recent reports have identified that formation of OG in G-rich regulatory elements in the promoters of the VEGF, TNFα, and SIRT1 genes can increase transcription via activation of the base excision repair (BER) pathway...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28613268/vitamin-e-modifies-high-fat-diet-induced-increase-of-dna-strand-breaks-and-changes-in-expression-and-dna-methylation-of-dnmt1-and-mlh1-in-c57bl-6j-male-mice
#4
Marlene Remely, Franziska Ferk, Sonja Sterneder, Tahereh Setayesh, Tatjana Kepcija, Sylvia Roth, Rahil Noorizadeh, Martina Greunz, Irene Rebhan, Karl-Heinz Wagner, Siegfried Knasmüller, Alexander Haslberger
Obesity is associated with low-grade inflammation, increased ROS production and DNA damage. Supplementation with antioxidants might ameliorate DNA damage and support epigenetic regulation of DNA repair. C57BL/6J male mice were fed a high-fat (HFD) or a control diet (CD) with and without vitamin E supplementation (4.5 mg/kg body weight (b.w.)) for four months. DNA damage, DNA promoter methylation and gene expression of Dnmt1 and a DNA repair gene (MLH1) were assayed in liver and colon. The HFD resulted in organ specific changes in DNA damage, the epigenetically important Dnmt1 gene, and the DNA repair gene MLH1...
June 14, 2017: Nutrients
https://www.readbyqxmd.com/read/28600325/hira-deficiency-in-muscle-fibers-causes-hypertrophy-and-susceptibility-to-oxidative-stress
#5
Nicolas Valenzuela, Benjamin Soibam, Lerong Li, Jing Wang, Lauren A Byers, Yu Liu, Robert J Schwartz, M David Stewart
Nucleosome assembly proceeds through DNA replication-coupled or replication-independent mechanisms. For skeletal myocytes, whose nuclei have permanently exited the cell cycle, replication-independent assembly is the only mode available for chromatin remodeling. For this reason, any nucleosome composition alterations accompanying transcriptional responses to physiological signals must occur through a DNA replication-independent pathway. HIRA is the histone chaperone primarily responsible for replication-independent incorporation of histone variant H3...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28582660/the-phytochemical-3-3-diindolylmethane-decreases-expression-of-ar-controlled-dna-damage-repair-genes-through-repressive-chromatin-modifications-and-is-associated-with-dna-damage-in-prostate-cancer-cells
#6
Zoraya Palomera-Sanchez, Gregory W Watson, Carmen P Wong, Laura M Beaver, David E Williams, Roderick H Dashwood, Emily Ho
Androgen receptor (AR) is a transcription factor involved in normal prostate physiology and prostate cancer (PCa) development. 3,3'-Diindolylmethane (DIM) is a promising phytochemical agent against PCa that affects AR activity and epigenetic regulators in PCa cells. However, whether DIM suppresses PCa via epigenetic regulation of AR target genes is unknown. We assessed epigenetic regulation of AR target genes in LNCaP PCa cells and showed that DIM treatment led to epigenetic suppression of AR target genes involved in DNA repair (PARP1, MRE11, DNA-PK)...
May 25, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28582417/genome-wide-alteration-in-dna-hydroxymethylation-in-the-sperm-from-bisphenol-a-exposed-men
#7
Huajun Zheng, Xiaoyu Zhou, De-Kun Li, Fen Yang, Hongjie Pan, Tianqi Li, Maohua Miao, Runsheng Li, Wei Yuan
Environmental BPA exposure has been shown to impact human sperm concentration and motility, as well as rodent spermatogenesis. However, it is unclear whether BPA exposure is associated with alteration in DNA hydroxymethylation, a marker for epigenetic modification, in human sperm. A genome-wide DNA hydroxymethylation study was performed using sperm samples of men who were occupationally exposed to BPA. Compared with controls who had no occupational BPA exposure, the total levels of 5-hydroxymethylcytosine (5hmc) increased significantly (19...
2017: PloS One
https://www.readbyqxmd.com/read/28576976/pleiotropic-and-adverse-effects-of-statins-do-epigenetics-play-a-role
#8
Stephanie C Allen, Cyril Ds Mamotte
Statins are widely used to prevent major cardiovascular events through the lowering of serum cholesterol. There is evidence that statins have pleiotropic effects, that is cholesterol-independent effects, that may also confer protection from cardiovascular disease and potentially numerous other pathologies including cancer. Statins also have a number of well described adverse effects including myopathy, rhabdomyolysis, liver damage and type 2 diabetes. This paper examines the evidence of epigenetic modifications as a contributory factor to the pleiotropic and adverse effects of statins...
June 2, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28575239/whole-genome-cardiac-dna-methylation-fingerprint-and-gene-expression-analysis-provide-new-insights-in-the-pathogenesis-of-chronic-chagas-disease-cardiomyopathy
#9
Laurie Laugier, Amanda Farage Frade, Frederico Moraes Ferreira, Monique Andrade Baron, Priscila Camillo Teixeira, Sandrine Cabantous, Ludmila Rodrigues Pinto Ferreira, Laurence Louis, Vagner Oliveira Carvalho Rigaud, Fabio Antônio Gaiotto, Fernando Bacal, Pablo Pomerantzeff, Edimar Bocchi, Jorge Kalil, Ronaldo Honorato Barros Santos, Edecio Cunha-Neto, Christophe Chevillard
Background: Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects 10 million people worldwide. Approximately 12,000 deaths attributable to Chagas disease occur annually due to Chagas disease cardiomyopathy (CCC), an inflammatory cardiomyopathy presenting with heart failure and arrythmia; 30% of infected subjects develop CCC years after infection. Genetic mechanisms play a role in differential progression to CCC, but little is known about the role of epigenetic modifications in pathological gene expression patterns in CCC patients' myocardium...
May 30, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28575157/sex-differences-in-aging-genomic-instability
#10
Kathleen E Fischer, Nicole C Riddle
Aging is characterized by decreasing physiological integration, reduced function, loss of resilience and increased risk of death. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist. While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal...
June 2, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28574327/intrinsic-line-1-hypomethylation-and-decreased-brca1-expression-are-associated-with-dna-repair-delay-in-irradiated-thyroid-cells
#11
Ricardo Cortez Cardoso Penha, Sheila Coelho Soares Lima, Mariana Boroni, Renata Ramalho-Oliveira, João P Viola, Denise Pires de Carvalho, Alfredo Fusco, Luis Felipe Ribeiro Pinto
Exposure to ionizing radiation greatly increases the risk of developing papillary thyroid carcinoma (PTC), especially during childhood, mainly due to gradual inactivation of DNA repair genes and DNA damages. Recent molecular characterization of PTC revealed DNA methylation deregulation of several promoters of DNA repair genes. Thus, epigenetic silencing might be a plausible mechanism for the activity loss of tumor suppressor genes in radiation-induced thyroid tumors. Herein, we investigated the impact of ionizing radiation on global methylation and CpG islands within promoter regions of homologous recombination (HR) and non-homologous end joining (NHEJ) genes, as well as its effects on gene expression, using two well-established normal differentiated thyroid cell lines (FRTL5 and PCCL3)...
June 2, 2017: Radiation Research
https://www.readbyqxmd.com/read/28551783/mitochondrial-mutations-in-cardiac-disorders
#12
Sung Ryul Lee, Jin Han
Mitochondria individually encapsulate their own genome, unlike other cellular organelles. Mitochondrial DNA (mtDNA) is a circular, double-stranded, 16,569-base paired DNA containing 37 genes: 13 proteins of the mitochondrial respiratory chain, two ribosomal RNAs (rRNAs; 12S and 16S), and 22 transfer RNAs (tRNAs). The mtDNA is more vulnerable to oxidative modifications compared to nuclear DNA because of its proximity to ROS-producing sites, limited presence of DNA damage repair systems, and continuous replication in the cell...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#13
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539453/epigenetic-metabolite-acetate-inhibits-class-i-ii-histone-deacetylases-promotes-histone-acetylation-and-increases-hiv-1-integration-in-cd4-t-cells
#14
Jean-François Bolduc, Laurent Hany, Corinne Barat, Michel Ouellet, Michel J Tremblay
In this study, we investigated the effect of acetate, the most concentrated short-chain fatty acid (SCFA) in the gut and bloodstream, on the susceptibility of primary human CD4(+) T cells to HIV-1 infection. We report that HIV-1 replication is increased in CD3/CD28-costimulated CD4(+) T cells upon acetate treatment. This enhancing effect correlates with an increased expression of the early activation marker CD69 and impaired class I/II histone deacetylase (HDAC) activity. In addition, acetate enhances acetylation of histones H3 and H4 and augments HIV-1 integration in the genome of CD4(+) T cells...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537880/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#15
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537256/design-of-synthetic-epigenetic-circuits-featuring-memory-effects-and-reversible-switching-based-on-dna-methylation
#16
Johannes A H Maier, Raphael Möhrle, Albert Jeltsch
Epigenetic systems store information in DNA methylation patterns in a durable but reversible manner, but have not been regularly used in synthetic biology. Here, we designed synthetic epigenetic memory systems using DNA methylation sensitive engineered zinc finger proteins to repress a memory operon comprising the CcrM methyltransferase and a reporter. Triggering by heat, nutrients, ultraviolet irradiation or DNA damaging compounds induces CcrM expression and DNA methylation. In the induced on-state, methylation in the operator of the memory operon prevents zinc finger protein binding leading to positive feedback and permanent activation...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#17
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28522752/mismatch-repair-proteins-initiate-epigenetic-alterations-during-inflammation-driven-tumorigenesis
#18
Ashley R Maiuri, Michael Peng, Shruthi Sriramkumar, Caitlin M Kamplain, Christina DeStefano Shields, Cynthia L Sears, Heather M O'Hagan
Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared to normal epithelium and non-inflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28504324/electromagnetic-fields-pulsed-radiofrequency-radiation-and-epigenetics-how-wireless-technologies-may-affect-childhood-development
#19
Cindy Sage, Ernesto Burgio
Mobile phones and other wireless devices that produce electromagnetic fields (EMF) and pulsed radiofrequency radiation (RFR) are widely documented to cause potentially harmful health impacts that can be detrimental to young people. New epigenetic studies are profiled in this review to account for some neurodevelopmental and neurobehavioral changes due to exposure to wireless technologies. Symptoms of retarded memory, learning, cognition, attention, and behavioral problems have been reported in numerous studies and are similarly manifested in autism and attention deficit hyperactivity disorders, as a result of EMF and RFR exposures where both epigenetic drivers and genetic (DNA) damage are likely contributors...
May 15, 2017: Child Development
https://www.readbyqxmd.com/read/28502747/chicken-egg-fetal-liver-dna-and-histopathologic-effects-of-structurally-diverse-carcinogens-and-non-carcinogens
#20
M J Iatropoulos, T Kobets, J-D Duan, K D Brunnemann, E Vock, U Deschl, G M Williams
Chicken egg fetal livers were evaluated for histopathological changes produced by four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2), benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non-carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of DNA adducts using the (32)P nucleotide postlabeling (NPL) assay and for DNA breaks using the comet assay...
May 11, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
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