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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/28101820/insulin-insulin-like-growth-factor-1-signalling-iis-based-regulation-of-lifespan-across-species
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28078645/parp-inhibitors-in-reproductive-system-cancers-current-use-and-developments
#4
REVIEW
Geraldine O'Sullivan Coyne, Alice P Chen, Robert Meehan, James H Doroshow
The repair of DNA damage is a critical cellular process governed by multiple biochemical pathways that are often found to be defective in cancer cells. The poly(ADP-ribose) polymerase (PARP) family of proteins controls response to single-strand DNA breaks by detecting these damaged sites and recruiting the proper factors for repair. Blocking this pathway forces cells to utilize complementary mechanisms to repair DNA damage. While PARP inhibition may not, in itself, be sufficient to cause tumor cell death, inhibition of DNA repair with PARP inhibitors is an effective cytotoxic strategy when it is used in patients who carry other defective DNA-repair mechanisms, such as mutations in the genes BRCA 1 and 2...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28068562/epigenetic-histopathological-and-transcriptomic-effects-following-exposure-to-depleted-uranium-in-adult-zebrafish-and-their-progeny
#5
Kewin Gombeau, Jean-Paul Bourdineaud, Jean-Luc Ravanat, Olivier Armant, Virginie Camilleri, Isabelle Cavalie, Magali Floriani, Christelle Adam-Guillermin
This study investigated the effects of adult zebrafish exposure to a nominal concentration of 20μgL(-1) of depleted uranium (DU) for six days upon DNA methylation, gene expression and the appearance of histopathological damage in their progeny. In the embryos at the 2-8 cell stage, the parental exposure induced significant DU accumulation, with levels seven times higher than those measured in the control embryos, but in larvae 96h post-fertilisation (hpf), uranium concentration had already returned to a level identical to that of the control larvae...
December 8, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/28061334/arginine-methylation-the-coming-of-age
#6
REVIEW
Roméo S Blanc, Stéphane Richard
Arginine methylation is a common post-translational modification functioning as an epigenetic regulator of transcription and playing key roles in pre-mRNA splicing, DNA damage signaling, mRNA translation, cell signaling, and cell fate decision. Recently, a wealth of studies using transgenic mouse models and selective PRMT inhibitors helped define physiological roles for protein arginine methyltransferases (PRMTs) linking them to diseases such as cancer and metabolic, neurodegenerative, and muscular disorders...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28044469/epigenetic-silencing-and-activation-of-transcription-influence-on-the-radiation-sensitivity-of-glioma-cell-lines
#7
A Sak, D Kübler, K Bannik, M Groneberg, S Strunz, R Kriehuber, M Stuschke
PURPOSE: To uncover the role of EZH2 and its opponent ASHL2, a polycomb and trithorax group protein, respectively on the radioresponsiveness of glioma cell lines. MATERIAL AND METHODS: Expression of EZH2 and ASHL2 was inhibited by siRNA in glioma cell lines. The effect on histone methylation, gene expression, DNA damage repair signaling, cell cycle checkpoints, apoptosis and tumor control were evaluated. RESULTS: Inhibition of EZH2 (EZH2i) led to a transcriptional dysregulation with upregulation of 544 and downregulation of 445 genes...
January 3, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28017527/dna-damage-repair-monitoring-and-epigenetic-dna-methylation-changes-in-seedlings-of-chernobyl-soybeans
#8
Mariyana Georgieva, Namik M Rashydov, Martin Hajduch
This pilot study was carried out to assess the effect of radio-contaminated Chernobyl environment on plant genome integrity 27 years after the accident. For this purpose, nuclei were isolated from root tips of the soybean seedlings harvested from plants grown in the Chernobyl area for seven generations. Neutral, neutral-alkaline, and methylation-sensitive comet assays were performed to evaluate the induction and repair of primary DNA damage and the epigenetic contribution to stress adaptation mechanisms. An increased level of single and double strand breaks in the radio-contaminated Chernobyl seedlings at the stage of primary root development was detected in comparison to the controls...
December 16, 2016: DNA Repair
https://www.readbyqxmd.com/read/28012783/epigenetic-regulation-of-redox-signaling-in-diabetic-retinopathy-role-of-nrf2
#9
REVIEW
Renu A Kowluru, Manish Mishra
Diabetic retinopathy is a major vision threatening disease among working age adults, and increased oxidative stress is one of the prime causative factors in its pathogenesis. Increased reactive oxygen species (ROS) in the cytosol damage mitochondria, and due to compromised antioxidant signaling system and dysfunctional mitochondria with damaged mitochondrial DNA, ROS continue to pile up, accelerating capillary cell loss. In addition to other cellular and enzymatic defense systems, the retina is also equipped with the nuclear erythroid-2-p45-related factor-2 (Nrf2) antioxidant response element signaling pathway, which controls the expression of genes important in detoxification and elimination of ROS...
December 22, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28001451/mgmt-hypomethylation-is-associated-with-dna-damage-in-workers-exposed-to-low-dose-benzene
#10
Jie Li, Xinjie Zhang, Zhini He, Qing Sun, Fei Qin, Zhenlie Huang, Xiao Zhang, Xin Sun, Linhua Liu, Liping Chen, Chen Gao, Shan Wang, Fangping Wang, Daochuan Li, Xiaowen Zeng, Qifei Deng, Qing Wang, Bo Zhang, Huanwen Tang, Wen Chen, Yongmei Xiao
OBJECTIVE: This study aims to assess the effects of low-dose benzene on DNA damage and MGMT methylation in occupational workers. MATERIALS AND METHODS: We recruited 96 non-smoking male petrochemical industry workers exposed to low-dose benzene and 100 matched control workers. Urinary S-phenylmercapturic acid (SPMA) and S-benzylmercapturic acid (SBMA) were measured for indicating internal exposure of benzene and toluene. The degree of DNA damage was determined by the Comet assay...
December 21, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/27995963/histone-deacetylase-inhibitors-mediate-dna-damage-repair-in-ameliorating-hemorrhagic-cystitis
#11
Subhash Haldar, Christopher Dru, Rajeev Mishra, Manisha Tripathi, Frank Duong, Bryan Angara, Ana Fernandez, Moshe Arditi, Neil A Bhowmick
Hemorrhagic cystitis is an inflammatory and ulcerative bladder condition associated with systemic chemotherapeutics, like cyclophosphomide. Earlier, we reported reactive oxygen species resulting from cyclophosphamide metabolite, acrolein, causes global methylation followed by silencing of DNA damage repair genes. Ogg1 (8-oxoguanine DNA glycosylase) is one such silenced base excision repair enzyme that can restore DNA integrity. The accumulation of DNA damage results in subsequent inflammation associated with pyroptotic death of bladder smooth muscle cells...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27989641/targeting-vascular-remodeling-to-treat-pulmonary-arterial-hypertension
#12
REVIEW
A A Roger Thompson, Allan Lawrie
Pulmonary arterial hypertension (PAH) describes a group of conditions with a common hemodynamic phenotype of increased pulmonary artery pressure, driven by progressive remodeling of small pulmonary arteries, leading to right heart failure and death. Vascular remodeling is the key pathological feature of PAH, but treatments targeting this process are lacking. In this review, we summarize important advances in our understanding of PAH pathogenesis from novel genetic and epigenetic factors, to cell metabolism and DNA damage...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27983682/zebrafish-as-an-in-vivo-model-to-assess-epigenetic-effects-of-ionizing-radiation
#13
REVIEW
Eva Yi Kong, Shuk Han Cheng, Kwan Ngok Yu
Exposure to ionizing radiations (IRs) is ubiquitous in our environment and can be categorized into "targeted" effects and "non-targeted" effects. In addition to inducing deoxyribonucleic acid (DNA) damage, IR exposure leads to epigenetic alterations that do not alter DNA sequence. Using an appropriate model to study the biological effects of radiation is crucial to better understand IR responses as well as to develop new strategies to alleviate exposure to IR. Zebrafish, Danio rerio, is a scientific model organism that has yielded scientific advances in several fields and recent studies show the usefulness of this vertebrate model in radiation biology...
December 15, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27982729/differential-dna-methylation-and-pm2-5-species-in-a-450k-epigenome-wide-association-study
#14
Lingzhen Dai, Amar Mehta, Irina Mordukhovich, Allan C Just, Jincheng Shen, Lifang Hou, Petros Koutrakis, David Sparrow, Pantel S Vokonas, Andrea A Baccarelli, Joel D Schwartz
Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27980098/restriction-glycosylases-involvement-of-endonuclease-activities-in-the-restriction-process
#15
Yingbiao Zhang, Tomoyuki Matsuzaka, Hirokazu Yano, Yoshikazu Furuta, Toshiaki Nakano, Ken Ishikawa, Masaki Fukuyo, Noriko Takahashi, Yutaka Suzuki, Sumio Sugano, Hiroshi Ide, Ichizo Kobayashi
All restriction enzymes examined are phosphodiesterases generating 3'-OH and 5'-P ends, but one restriction enzyme (restriction glycosylase) excises unmethylated bases from its recognition sequence. Whether its restriction activity involves endonucleolytic cleavage remains unclear. One report on this enzyme, R.PabI from a hyperthermophile, ascribed the breakage to high temperature while another showed its weak AP lyase activity generates atypical ends. Here, we addressed this issue in mesophiles. We purified R...
December 14, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27977688/regulation-of-the-human-telomerase-gene-tert-by-telomere-position-effect-over-long-distances-tpe-old-implications-for-aging-and-cancer
#16
Wanil Kim, Andrew T Ludlow, Jaewon Min, Jerome D Robin, Guido Stadler, Ilgen Mender, Tsung-Po Lai, Ning Zhang, Woodring E Wright, Jerry W Shay
Telomerase is expressed in early human development and then becomes silenced in most normal tissues. Because ~90% of primary human tumors express telomerase and generally maintain very short telomeres, telomerase is carefully regulated, particularly in large, long-lived mammals. In the current report, we provide substantial evidence for a new regulatory control mechanism of the rate limiting catalytic protein component of telomerase (hTERT) that is determined by the length of telomeres. We document that normal, young human cells with long telomeres have a repressed hTERT epigenetic status (chromatin and DNA methylation), but the epigenetic status is altered when telomeres become short...
December 2016: PLoS Biology
https://www.readbyqxmd.com/read/27951449/plant-flavonoids-in-cancer-chemoprevention-role-in-genome-stability
#17
REVIEW
Vazhappilly Cijo George, Graham Dellaire, H P Vasantha Rupasinghe
Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer...
November 28, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27935057/crosstalk-among-uv-induced-inflammatory-mediators-dna-damage-and-epigenetic-regulators-facilitates-suppression-of-the-immune-system
#18
Ram Prasad, Santosh K Katiyar
The suppression of the immune system by overexposure to ultraviolet (UV) radiation has been implicated in the initiation and progression of photocarcinogenesis. Numerous changes occur in the skin on UVB exposure, including the generation of inflammatory mediators, DNA damage, epigenetic modifications, and migration and functional alterations in the antigen-presenting dendritic cells. Although each of these alterations can elicit a cascade of events that have the potential to modulate immune sensitivity alone, there is emerging evidence that there is considerable crosstalk between these cascades...
December 9, 2016: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/27933097/molecular-mechanisms-of-hpv-mediated-neoplastic-progression
#19
REVIEW
Rashmirani Senapati, Nihar Nalini Senapati, Bhagirathi Dwibedi
Human Papillomavirus is the major etiological agent in the development of cervical cancer but not a sufficient cause. Despite significant research, the underlying mechanisms of progression from a low-grade squamous intraepithelial lesion to high grade squamous intraepithelial lesion are yet to be understood. Deregulation of viral gene expression and host genomic instability play a central role in virus-mediated carcinogenesis. Key events such as viral integration and epigenetic modifications may lead to the deregulation of viral and host gene expression...
2016: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/27914347/differential-crosstalk-between-global-dna-methylation-and-metabolomics-associated-with-cell-type-specific-stress-response-by-pristine-and-functionalized-mwcnt
#20
Nivedita Chatterjee, Jisu Yang, Dahye Yoon, Suhkmann Kim, Sang-Woo Joo, Jinhee Choi
The present study endeavored to evaluate the comprehensive mechanisms of MWCNT-induced toxicity with particular emphasis on understanding cell specificity in relation to surface functionalization of MWCNT. Following treatment with differentially functionalized (hydroxylation/carboxylation) MWCNT on human bronchial epithelial (BEAS-2B) and human hepatoma (HepG2) cell lines, intracellular uptake, various toxicological end points, global metabolomics profiling and DNA methylation were evaluated. Herein, the comparative in vitro studies ascertained that surface functionalization diminished the toxic potentiality of MWCNT in respect of their pristine counterpart...
January 2017: Biomaterials
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