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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/28213404/hydrogen-sulfide-alleviates-hypertensive-kidney-dysfunction-through-an-epigenetic-mechanism
#1
Gregory Weber, Sathnur Pushpakumar, Utpal Sen
Hypertension is a major risk factor for chronic kidney disease (CKD) and renal inflammation is an integral part in this pathology. Hydrogen sulfide (H2S) has been shown to mitigate renal damage through reduction in blood pressure and reactive oxygen species; however, the exact mechanisms are not clear. While several studies have underlined the role of epigenetics in renal inflammation and dysfunction, the mechanisms through which epigenetic regulators play role in hypertension are not well defined. In this study, we sought to identify if microRNAs are dysregulated in response to angiotensin-II (Ang-II) induced hypertension in the kidney and whether H2S donor, GYY 4137, could reverse the microRNA alteration and kidney function...
February 17, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28186195/cenp-a-chromatin-disassembly-in-stressed-and-senescent-murine-cells
#2
Sabrine Hédouin, Giacomo Grillo, Ivana Ivkovic, Guillaume Velasco, Claire Francastel
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong and selective transcriptional activation of centromeric repeats is detected within hours. This is followed by disorganization of centromeres with striking delocalization of nucleosomal CENP-A, the key determinant of centromere identity and function, in a mechanism requiring active transcription of centromeric repeats, the DNA Damage Response (DDR) effector ATM and chromatin remodelers/histone chaperones...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184298/recent-advances-in-understanding-assessing-toxicity-to-the-epigenome
#3
REVIEW
Kevin Sweder
The ability of non-genotoxic agents to induce cancer has been documented and clearly requires a reassessment of testing for environmental and human safety. Drug safety testing has historically relied on test batteries designed to detect DNA damage leading to mutation and cancer. The standard genetic toxicology testing battery has been a reliable tool set to identify small molecules/chemicals as hazards that could lead to genetic changes in organisms and induction of cancer. While pharmaceutical companies and regulatory agencies have extensively used the standard battery, it is not suitable for compounds that may induce epigenetic changes...
2017: F1000Research
https://www.readbyqxmd.com/read/28179585/oncogenomic-disruptions-in-arsenic-induced-carcinogenesis
#4
REVIEW
Adam P Sage, Brenda C Minatel, Kevin W Ng, Greg L Stewart, Trevor J B Dummer, Wan L Lam, Victor D Martinez
Chronic exposure to arsenic affects more than 200 million people worldwide, and has been associated with many adverse health effects, including cancer in several organs. There is accumulating evidence that arsenic biotransformation, a step in the elimination of arsenic from the human body, can induce changes at a genetic and epigenetic level, leading to carcinogenesis. At the genetic level, arsenic interferes with key cellular processes such as DNA damage-repair and chromosomal structure, leading to genomic instability...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179395/molecular-physiology-of-freeze-tolerance-in-vertebrates
#5
REVIEW
Kenneth B Storey, Janet M Storey
Freeze tolerance is an amazing winter survival strategy used by various amphibians and reptiles living in seasonally cold environments. These animals may spend weeks or months with up to ∼65% of their total body water frozen as extracellular ice and no physiological vital signs, and yet after thawing they return to normal life within a few hours. Two main principles of animal freeze tolerance have received much attention: the production of high concentrations of organic osmolytes (glucose, glycerol, urea among amphibians) that protect the intracellular environment, and the control of ice within the body (the first putative ice-binding protein in a frog was recently identified), but many other strategies of biochemical adaptation also contribute to freezing survival...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28177898/maternal-dietary-zinc-supplementation-enhances-the-epigenetic-activated-antioxidant-ability-of-chick-embryos-from-maternal-normal-and-high-temperatures
#6
Yongwen Zhu, Xiudong Liao, Lin Lu, Wenxiang Li, Liyang Zhang, Cheng Ji, Xi Lin, Hsiao-Ching Liu, Jack Odle, Xugang Luo
The role of maternal dietary zinc supplementation in protecting the embryos from maternal hyperthermia-induced negative effects via epigenetic mechanisms was examined using an avian model (Gallus gallus). Broiler breeder hens were exposed to two maternal temperatures (21°C and 32°C) × three maternal dietary zinc treatments (zinc-unsupplemented control diet, the control diet + 110 mg zinc/kg inorganic or organic zinc) for 8 weeks. Maternal hyperthermia increased the embryonic mortality and induced oxidative damage evidenced by the elevated mRNA expressions of heat shock protein genes...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28167130/genotoxicity-of-lipid-oxidation-compounds
#7
REVIEW
Peter M Eckl, Nikolaus Bresgen
Lipid peroxidation, the oxidative degradation of membrane lipids by reactive oxygen species generates a large variety of breakdown products such as alkanes, aldehydes, ketones, alcohols, furans and others. Due to their reactivity aldehydes (alkanals, 2-alkenals, 2,4-alkadienals, 4-hydroxyalkenals) received a lot of attention, in particular because they can diffuse from the site of formation and interact with proteins and nucleic acids thus acting as second toxic messengers. The major aldehydic peroxidation product of membrane lipids is 4-hydroxynonenal (HNE)...
February 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28166834/downregulation-of-mir-130b-301b-cluster-is-mediated-by-aberrant-promoter-methylation-and-impairs-cellular-senescence-in-prostate-cancer
#8
João Ramalho-Carvalho, Inês Graça, Antonio Gomez, Jorge Oliveira, Rui Henrique, Manel Esteller, Carmen Jerónimo
BACKGROUND: Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. METHODS: Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip...
February 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28150947/sequencing-the-mouse-genome-for-the-oxidatively-modified-base-8-oxo-7-8-dihydroguanine-by-og-seq
#9
Yun Ding, Aaron M Fleming, Cynthia J Burrows
Oxidatively derived damage to the genome can yield the base 8-oxo-7,8-dihydroguanine (OG). In vitro studies hypothesized OG would preferentially form in 5`-GG-3` sequence contexts when the genome is exposed to reactive oxygen species. Herein, OG locations in the genome were studied by development and implementation of "OG-Seq" to sequence OG sites via next-generation sequencing at ~0.15-kb resolution. The results of this study found ~10,000 regions of OG enrichment in WT mouse embryonic fibroblasts (MEFs) and ~18,000 regions when the OG repair glycosylase Ogg1 was knocked out...
February 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28143930/oxidative-dna-damage-is-epigenetic-by-regulating-gene-transcription-via-base-excision-repair
#10
Aaron M Fleming, Yun Ding, Cynthia J Burrows
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex-forming sequences (PQS) in promoter-coding strands, initiating base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1), yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (VEGF) or endonuclease III-like protein 1 (NTHL1) genes...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28141798/oxidative-dna-damage-induces-hypomethylation-in-a-compromised-base-excision-repair-colorectal-tumourigenesis
#11
Daniela Furlan, Davide Trapani, Enrico Berrino, Carla Debernardi, Mara Panero, Laura Libera, Nora Sahnane, Cristina Riva, Maria Grazia Tibiletti, Fausto Sessa, Anna Sapino, Tiziana Venesio
BACKGROUND: A compromised base excision repair (BER) promotes carcinogenesis by accumulating oxidative DNA-damaged products as observed in MUTYH-associated polyposis, a hereditary colorectal cancer syndrome marked by adenomas and cancers with an accumulation of 8-oxoguanine. Remarkably, DNA global demethylation has been shown to be mediated by BER, suggesting a relevant interplay with early colorectal tumourigenesis. To check this hypothesis, we investigated a cohort of 49 adenomas and 10 carcinomas, derived from 17 MUTYH-associated polyposis patients; as adenoma controls, we used a set of 36 familial adenomatous polyposis and 24 sporadic polyps...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28133504/egcg-prevents-high-fat-diet-induced-changes-in-gut-microbiota-decreases-of-dna-strand-breaks-and-changes-in-expression-and-dna-methylation-of-dnmt1-and-mlh1-in-c57bl-6j-male-mice
#12
Marlene Remely, Franziska Ferk, Sonja Sterneder, Tahereh Setayesh, Sylvia Roth, Tatjana Kepcija, Rahil Noorizadeh, Irene Rebhan, Martina Greunz, Johanna Beckmann, Karl-Heinz Wagner, Siegfried Knasmüller, Alexander G Haslberger
Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression of DNA methyltransferase 1, interleukin 6, and MutL homologue 1 were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28131900/non-coding-rnas-and-neuroprotection-after-acute-cns-injuries
#13
Raghavendar Chandran, Suresh L Mehta, Raghu Vemuganti
Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide...
January 26, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28129654/time-dependent-modulation-of-tumor-radiosensitivity-by-a-pan-hdac-inhibitor-abexinostat
#14
Sofia Rivera, Céline Leteur, Frédérique Mégnin, Frédéric Law, Isabelle Martins, Ioana Kloos, Stéphane Depil, Nazanine Modjtahedi, Jean Luc Perfettini, Christophe Hennequin, Eric Deutsch
Despite prominent role of radiotherapy in lung cancer management, there is an urgent need for strategies increasing therapeutic efficacy. Reversible epigenetic changes are promising targets for combination strategies using HDAC inhibitors (HDACi).Here we evaluated on two NSCLC cell lines, the antitumor effect of abexinostat, a novel pan HDACi combined with irradiation in vitro in normoxia and hypoxia, by clonogenic assays, demonstrating that abexinostat enhances radiosensitivity in a time dependent way with mean SER10 between 1...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28124145/role-of-oxidative-stress-in-epigenetic-modification-of-mmp-9-promoter-in-the-development-of-diabetic-retinopathy
#15
Renu A Kowluru, Yang Shan
BACKGROUND: In the pathogenesis of diabetic retinopathy, damaged retinal mitochondria accelerate apoptosis of retinal capillary cells, and regulation of oxidative stress by manipulating mitochondrial superoxide dismutase (SOD2) protects mitochondrial homeostasis and prevents the development of diabetic retinopathy. Diabetes also activates matrix metalloproteinase-9 (MMP-9), and activated MMP-9 damages retinal mitochondria. Recent studies have shown a dynamic DNA methylation process playing an important role in regulation of retinal MMP-9 transcription in diabetes; the aim of this study is to investigate the role of oxidative stress in MMP-9 transcription...
January 25, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28119128/the-toxic-effects-of-chlorophenols-and-associated-mechanisms-in-fish
#16
REVIEW
Tingting Ge, Jiangyuan Han, Yongmei Qi, Xueyan Gu, Lin Ma, Chen Zhang, Sajid Naeem, Dejun Huang
Chlorophenols (CPs) are ubiquitous contaminants in the environment primarily released from agricultural and industrial wastewater. These compounds are not readily degraded naturally, and easily accumulate in organs, tissues and cells via food chains, further leading to acute and chronic toxic effects on aquatic organisms. Herein, we review the available literature regarding CP toxicity in fish, with special emphasis on the potential toxic mechanisms. CPs cause oxidative stress via generation of reactive oxygen species, induction of lipid peroxidation and/or oxidative DNA damage along with inhibition of antioxidant systems...
March 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28111205/carcinogenic-risk-and-bisphenol-a-exposure-a-focus-on-molecular-aspects-in-endoderm-derived-glands
#17
Danila Cuomo, Immacolata Porreca, Gilda Cobellis, Roberta Tarallo, Giovanni Nassa, Geppino Falco, Antonio Nardone, Francesca Rizzo, Massimo Mallardo, Concetta Ambrosino
Epidemiological and experimental evidence associates the exposure to Bisphenol A with the increase of cancer risk in several organs, including prostate. BPA targets different pathways involved in carcinogenicity including the Nuclear Receptors (i.e. estrogen and androgen receptors), stress regulated proteins and, finally, epigenetic changes. Here, we analyse BPA-dependent carcinogenesis in endoderm-derived glands, thyroid, liver, pancreas and prostate focusing on cell signalling, DNA damage repair pathways and epigenetic modifications...
January 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#18
REVIEW
Rebecca Mathew, Manika Pal Bhadra, Utpal Bhadra
An organism's well-being is facilitated by numerous molecular and biochemical pathways that ensure homeostasis within cells and tissues. Aging causes a gradual let-down in the maintenance of homeostasis due to various endogenous and environmental challenges, leading to amassing of damages, functional deterioration of different tissues and vulnerability to ailments. Nutrient sensing pathways that maintain glucose homeostasis in body are involved in regulation of aging. Insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) pathway was the first nutrient sensing pathway discovered to affect the aging process...
January 18, 2017: Biogerontology
https://www.readbyqxmd.com/read/28100624/azacytidine-treatment-inhibits-the-progression-of-herpes-stromal-keratitis-by-enhancing-regulatory-t-cell-function
#19
Siva Karthik Varanasi, Pradeep B J Reddy, Siddheshvar Bhela, Ujjaldeep Jaggi, Fernanda Gimenez, Barry T Rouse
: Ocular infection with Herpes Simplex Virus type 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance as well as chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit Stromal Keratitis (SK) lesion severity. In this report, we have explored the novel approach of inhibiting DNA methyltransferase activity using 5-Azacytidine (cytosine analog) to limit HSV-1 induced ocular lesions...
January 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28096241/the-chromodomain-helicase-dna-binding-chromatin-remodelers-family-traits-that-protect-from-and-promote-cancer
#20
Alea A Mills
A plethora of mutations in chromatin regulators in diverse human cancers is emerging, attesting to the pivotal role of chromatin dynamics in tumorigenesis. A recurrent theme is inactivation of the chromodomain helicase DNA-binding (CHD) family of proteins-ATP-dependent chromatin remodelers that govern the cellular machinery's access to DNA, thereby controlling fundamental processes, including transcription, proliferation, and DNA damage repair. This review highlights what is currently known about how genetic and epigenetic perturbation of CHD proteins and the pathways that they regulate set the stage for cancer, providing new insight for designing more effective anti-cancer therapies...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
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