scholarly journals Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline

Genetics ◽  
2019 ◽  
Vol 214 (2) ◽  
pp. 381-395 ◽  
Author(s):  
Maria Fernanda Hornos Carneiro ◽  
Nara Shin ◽  
Rajendiran Karthikraj ◽  
Fernando Barbosa ◽  
Kurunthachalam Kannan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Bisphenol A ◽  
Oxidative Dna Damage ◽  
Low Cost ◽  
Endocrine Disrupting Chemicals ◽  
Human Reproductive ◽  
Low Cost Strategy ◽  
The Impact

Endocrine-disrupting chemicals are ubiquitously present in our environment, but the mechanisms by which they adversely affect human reproductive health and strategies to circumvent their effects remain largely unknown. Here, we show in Caenorhabditis elegans that supplementation with the antioxidant Coenzyme Q10 (CoQ10) rescues the reprotoxicity induced by the widely used plasticizer and endocrine disruptor bisphenol A (BPA), in part by neutralizing DNA damage resulting from oxidative stress. CoQ10 significantly reduces BPA-induced elevated levels of germ cell apoptosis, phosphorylated checkpoint kinase 1 (CHK-1), double-strand breaks (DSBs), and chromosome defects in diakinesis oocytes. BPA-induced oxidative stress, mitochondrial dysfunction, and increased gene expression of antioxidant enzymes in the germline are counteracted by CoQ10. Finally, CoQ10 treatment also reduced the levels of aneuploid embryos and BPA-induced defects observed in early embryonic divisions. We propose that CoQ10 may counteract BPA-induced reprotoxicity through the scavenging of reactive oxygen species and free radicals, and that this natural antioxidant could constitute a low-risk and low-cost strategy to attenuate the impact on fertility by BPA.

scholarly journals Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline”

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 879-890
Author(s):  
Beatrix R. Bradford ◽  
Nicole E. Briand ◽  
Nina Fassnacht ◽  
Esabelle D. Gervasio ◽  
Aidan M. Nowakowski ◽  
...  
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Bisphenol A ◽  
Coenzyme Q10 ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Fluorescent Microscopy ◽  
Environmental Chemicals ◽  
Background Information ◽  
Environmental Toxicants

Environmental toxicants are chemicals that negatively affect human health. Although there are numerous ways to limit exposure, the ubiquitous nature of certain environmental toxicants makes it impossible to avoid them entirely. Consequently, scientists are continuously working toward developing strategies for combating their harmful effects. Using the nematode Caenorhabditis elegans, a model with many genetic and physiological similarities to humans, researchers in the Colaiácovo laboratory have identified several molecular mechanisms by which the toxic agent bisphenol A (BPA) interferes with reproduction. Here, we address their recent discovery that a widely available compound, Coenzyme Q10 (CoQ10), can rescue BPA-induced damage. This work is significant in that it poses a low-cost method for improving reproductive success in humans. The goal of this primer is to assist educators and students with navigating the paper entitled “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline.” It is ideally suited for integration into an upper-level undergraduate course such as Genetics, Cell and Molecular Biology, Developmental Biology, or Toxicology. The primer provides background information on the history of BPA, the utility of the C. elegans germ line as a model for studying reproductive toxicity, and research methods including assessment of programmed cell death, fluorescent microscopy applications, and assays to quantify gene expression. Questions for deeper exploration in-class or online are provided.Related article in GENETICS: Hornos Carneiro MF, Shin N, Karthikraj R, Barbosa F Jr, Kannan K, Colaiácovo MP. Antioxidant CoQ10 restores fertility by rescuing bisphenol A-induced oxidative DNA damage in the Caenorhabditis elegans Germline. Genetics 214:381–395.

scholarly journals Oxidative stress in thyroid carcinomas: biological and clinical significance

2019 ◽  
Vol 26 (3) ◽  
pp. R131-R143 ◽  
Author(s):  
Rabii Ameziane El Hassani ◽  
Camille Buffet ◽  
Sophie Leboulleux ◽  
Corinne Dupuy
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Genomic Instability ◽  
Oxidative Dna Damage ◽  
Cell Transformation ◽  
Second Messengers ◽  
Cellular Functions ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
The Impact

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability. Indeed, one particularity of this organ is that follicular thyroid cells synthesise thyroid hormones through a complex mechanism that requires H2O2. Because of their detection in thyroid adenomas and in early cell transformation, both oxidative stress and DNA damage are believed to be neoplasia-preceding events in thyroid cells. Oxidative DNA damage is, in addition, detected in the advanced stages of thyroid cancer, suggesting that oxidative lesions of DNA also contribute to the maintenance of genomic instability during the subsequent phases of tumourigenesis. Finally, ionizing radiation and the mutation of oncogenes, such as RAS and BRAF, play a key role in thyroid carcinogenesis through separate and unique mechanisms: they upregulate the expression of two distinct ‘professional’ ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, which cause DNA damage that may promote chromosomal instability, tumourigenesis and dedifferentiation.

scholarly journals ‘Liver let die’: oxidative DNA damage and hepatotropic viruses

2014 ◽  
Vol 95 (5) ◽  
pp. 991-1004 ◽  
Author(s):  
Martin R. Higgs ◽  
Philippe Chouteau ◽  
Hervé Lerat
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Large Body ◽  
Clinical Importance ◽  
Dna Lesions ◽  
Chronic Infections ◽  
The Impact

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700 000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.

Serum of 8-OHdG as a potential biomarker of oxidative DNA damage in workers exposed to harmful working environments

2020 ◽  
pp. 783-783
Author(s):  
I. A. Umnyagina ◽  
L. A. Strakhova ◽  
T. V. Blinova
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Blood Serum ◽  
Oxidative Dna Damage ◽  
Working Environment ◽  
Working Environments ◽  
Potential Biomarker ◽  
High Level ◽  
Damage Marker

In the blood serum of 70% individuals exposed to harmful factors of the working environment, a high level of oxidative stress and the DNA damage marker 8-Hydroxy-2’-Deoxyguanosine (8-OHdG) were detected.

Abstract 424: Vascular Smooth Muscle Cell Expression of S100a12 in Vivo Induces Enhanced Oxidative Stress & Vascular Remodeling

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Jeannine Wilk ◽  
Gene Kim ◽  
Yanmin Zhang ◽  
Jalees Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Smooth Muscle ◽  
Vascular Remodeling ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Brdu Incorporation ◽  
Elastic Fibers ◽  
Nuclear Staining

S100A12 is a small calcium binding protein that is a signal transduction ligand of the receptor for advance glycation endproducts (RAGE). S100A12, like RAGE, is expressed in the vessel wall of atherosclerotic vasculature, particularly in smooth muscle cells (SMC). While RAGE has been extensively implicated in inflammatory states such as atherosclerosis, the role of S100A12 is less clear. We tested the hypothesis that expression of human S100A12 directly exacerbates vascular inflammation. Several lines of Bl6/J transgenic mice (tg) expressing human S100A12 in SMC under control of the SM22a promoter were generated. Primary aortic SMC from tg and wild type (wt) littermates were isolated and analyzed for (i) proliferation using MTS/Formazan Assay and BrdU incorporation, (ii) oxidative stress using using flow cytometry with MitoSOX antibody, oxidative DNA damage using immunofluorescence microscopy with anti-8-oxo-dG antibody, and NF-kB activation measured by EMSA and (iii) cytokine expression measured by IL-6 ELISA. Furthermore, the aortas from tg and wt mice were examined. Results: Tg but not wt SMC expressed S100A12 protein. Tg SMC had a significant 1.9 to 2.7 fold increase in conversion of MTS into Formazan at 24–96 hours likely reflective of increased metabolic activity since BrdU incorporation into DNA was less in tg compared to wt SMC (4% vs 21% positive BrdU nuclei, p <0.05). Tg SMC showed significantly higher levels of mitochondrial generated ROS, nuclear staining for oxidative DNA damage which was not detected in the nuclei of wt SMC’s, and a 2.5 fold increase in NFkB activity. IL-6 production at baseline was higher in tg SMC’s (615 vs 213 pg/ml, p< 0.05) and increased dramatically after LPS treatment (10 ng/ml) in tg SMC’s (2130 vs 415 pg/ml). Histologic examination of the thoracic aorta at 10 weeks of age revealed increased collagen deposition in the aortic media with fragmentation and disarray of elastic fibers. In vivo ultrasound revealed a progressive dilation of the aortic arch from age 10 weeks to 16 weeks of age (1.27 to 1.60 mm, p<0.05) in tg but not in wt littermate mice (1.30 to 1.33 mm, p=0.1). These data reveal the novel finding that targeted expression of human S100A12 in SMC modulates oxidative stress, inflammation and vascular remodeling.

ID: 140: KLOTHO, AN ANTI-AGING MOLECULE, REGULATES ALVEOLAR EPITHELIAL CELL MTDNA DAMAGE AND APOPTOSIS

2016 ◽  
Vol 64 (4) ◽  
pp. 961.1-961
Author(s):  
S Kim ◽  
P Cheresh ◽  
RP Jablonski ◽  
DW Kamp ◽  
M Eren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Oxidative Dna Damage ◽  
Alveolar Epithelial Cell ◽  
Premature Aging ◽  
Protective Effects ◽  
Mtdna Damage ◽  
Alveolar Epithelial

RationaleConvincing evidence has emerged that impaired alveolar epithelial cell (AEC) injury and repair resulting from ‘exaggerated’ lung aging and mitochondrial dysfunction are critical determinants of the lung fibrogenic potential of toxic agents, including asbestos fibers, but the mechanisms underlying these findings is unknown. We showed that the extent of AEC mitochondrial DNA (mtDNA) damage and apoptosis are critical determinants of asbestos-induced pulmonary fibrosis (Cheresh et al AJRCMB 2014, Kim et al JBC 2014). Klotho is an age-inhibiting gene and Klotho-deficient mice demonstrate a premature aging phenotype that includes a reduced lifespan, arteriosclerosis, and lung oxidative DNA damage, and that Klotho attenuates hyperoxic-induced AEC DNA damage and apoptosis (Ravikumar et al AJP-Lung 2014). We reason that Klotho has an important role in limiting pulmonary fibrosis by protecting the AECs from oxidative stress.MethodsQuantitative PCR-based measurement of mtDNA damage was assessed following transient transfection with wild-type Klotho, Klotho siRNA or AKT siRNA in A549 and/or MLE-12 cells for 48 hrs followed by exposure to either amosite asbestos (25 µg/cm2) or H2O2 (200 µM) for 24 hrs. Apoptosis was assessed by cleaved caspase-9/3 levels and DNA fragmentation assay. Murine pulmonary fibrosis was analyzed in male 8–10 week old WT (C3H/C57B6J) mice or Klotho heterozygous knockout (Kl+/−) mice following intratracheal instillation of a single dose of 100 µg crocidolite asbestos or titanium dioxide (negative control) using histology (fibrosis score by Masson's trichrome staining) and lung collagen (Sircoll assay).ResultsCompared to control, amosite asbestos or H2O2 reduces Klotho mRNA/protein expression. Notably, silencing of Klotho promotes oxidative stress-induced AEC mtDNA damage and apoptosis whereas Klotho-enforced expression (EE) and Euk-134, a mitochondrial ROS scavenger, are protective. Interestingly, Kl+/− mice have increased asbestos-induced lung fibrosis. Also, we find that inhibition or silencing of AKT augments oxidant-induced AEC mtDNA damage and apoptosis.ConclusionsOur data demonstrate a crucial role for AEC AKT signaling in mediating the mtDNA damage protective effects of Klotho. Given the importance of AEC aging and apoptosis in pulmonary fibrosis, we reason that Klotho/AKT axis is an innovative therapeutic target for preventing common lung diseases of aging (i.e. IPF, COPD, lung cancer, etc.) for which more effective management regimens are clearly needed.FundingNIH-RO1 ES020357-01A1 (DK) and VA Merit (DK).

scholarly journals ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses

2017 ◽  
Vol 372 (1731) ◽  
pp. 20160283 ◽  
Author(s):  
N. Daniel Berger ◽  
Fintan K. T. Stanley ◽  
Shaun Moore ◽  
Aaron A. Goodarzi
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Strand Break ◽  
Chromatin Remodelling ◽  
Double Strand Breaks ◽  
Biochemical Network ◽  
Regulatory Function ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
The Impact

Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system. This article is part of the themed issue ‘Chromatin modifiers and remodellers in DNA repair and signalling’.

scholarly journals Potential role of oxidative DNA damage in the impact of PNPLA3 variant (rs 738409 C>G) in hepatocellular carcinoma risk

Hepatology ◽  
2014 ◽  
Vol 60 (3) ◽  
pp. 1110-1111 ◽  
Author(s):  
Emeric Limagne ◽  
Vanessa Cottet ◽  
Alexia Karen Cotte ◽  
Samia Hamza ◽  
Patrick Hillon ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Potential Role ◽  
The Impact ◽  
Carcinoma Risk

scholarly journals Small molecule inhibitor of OGG1 blocks oxidative DNA damage repair at telomeres and potentiates Methotrexate anticancer effects

2020 ◽  
Author(s):  
Juan Miguel Baquero ◽  
Carlos Benítez-Buelga ◽  
Varshni Rajagopal ◽  
Zhao Zhenjun ◽  
Raúl Torres-Ruiz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Lines ◽  
Small Molecule ◽  
Oxidative Dna Damage ◽  
Genome Instability ◽  
Excision Repair ◽  
Small Molecule Inhibitor ◽  
Osteosarcoma Cell ◽  
Molecule Inhibitor

Abstract Background: The most common oxidative DNA lesion is 8-oxoguanine (8-oxoG) which is mainly recognized and excised by the glycosylase OGG1, initiating the Base Excision Repair (BER) pathway. Telomeres are particularly sensitive to oxidative stress which disrupts telomere homeostasis triggering genome instability. Methods: We used U2OS OGG1-GFP osteosarcoma cell line to study the role of OGG1 at the telomeres in response to oxidative stress. Next, we investigated the effects of inactivating pharmacologically the BER during oxidative stress (OS) conditions by using a specific small molecule inhibitor of OGG1 (TH5487) in different human cell lines. Results: We have found that during OS, TH5487 effectively blocks BER initiation at telomeres causing accumulation of oxidized bases at this region, correlating with other phenotypes such as telomere losses, micronuclei formation and mild proliferation defects. Besides, the antimetabolite Methotrexate synergizes with TH5487 through induction of intracellular ROS formation, which potentiates TH5487 mediated telomere and genome instability in different cell lines. Conclusions: Our findings demonstrate that OGG1 is required to protect telomeres from OS and present OGG1 inhibitors as a tool to induce oxidative DNA damage at telomeres, with the potential for developing new combination therapies for cancer treatment.

scholarly journals Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus

2011 ◽  
Vol 34 (3) ◽  
pp. 163 ◽  
Author(s):  
Omur Tabak ◽  
Remise Gelisgen ◽  
Hayriye Erman ◽  
Fusun Erdenen ◽  
Cüneyt Muderrisoglu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Vascular Complications ◽  
Diabetic Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Serum Samples ◽  
Type 2 Diabetic Patients

Purpose: The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters. Methods: The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2’deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, Nε-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied. Results: 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications. Conclusions: Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.

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