DNA hypomethylation and oxidative stress-mediated increase in genomic instability in equine sarcoid-derived fibroblasts.
Abstract: It is widely accepted that equine sarcoid disease, the most common skin associated neoplasm in equids, is induced by bovine papillomavirus (BPV-1). Although BPV-1 DNA has been found in almost all examined sarcoids so far, its detailed impact on the horse's host cell metabolism is largely unknown. We used equine fibroblast cell lines originating from sarcoid biopsies to study BPV-1-associated changes on DNA methylation status and oxidative stress parameters. Sarcoid-derived fibroblasts manifested increased proliferation in vitro, transcriptional rDNA activity (NORs expression) and DNA hypomethylation compared to control cells. Cells isolated from equine sarcoids suffered from oxidative stress: the expression of antioxidant enzymes was decreased and the superoxide production was increased. Moreover, increased ploidy, oxidative DNA damage and micronuclei formation was monitored in sarcoid cells. We postulate that both altered DNA methylation status and redox milieu may affect genomic stability in BPV-1-infected cells and in turn contribute to sarcoid pathology.
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Publication Date: 2012-05-29 PubMed ID: 22659572DOI: 10.1016/j.biochi.2012.05.026Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research dives into the effects of the bovine papillomavirus (BPV-1) on horses, particularly its impact on equine sarcoid disease. The study uses fibroblasts from sarcoid biopsies to examine changes in DNA methylation status and oxidative stress elements linked to BPV-1.
Understanding Equine Sarcoid Disease and BPV-1
- The study centres around equine sarcoid disease, the most prevalent skin-related neoplasm in equines, predominantly caused by the bovine papillomavirus (BPV-1).
- While the presence of BPV-1 DNA has been confirmed nearly universally in sarcoids, the exact effect it has on the metabolism of equine host cells remains relatively unexplored.
Key Observations in Sarcoid-Derived Fibroblasts
- The researchers discovered that fibroblasts derived from sarcoids exhibited increased in-vitro proliferation, heightened transcriptional rDNA activity as well as DNA hypomethylation when compared to control cells.
- These sarcoid cells also showed signs of oxidative stress, characterized by the decreased expression of antioxidant enzymes and increased superoxide production.
Impacts on Genomic Stability
- Sarcoid cells exhibited increased ploidy, oxidative DNA damage and the formation of micronuclei indicating a higher genomic instability.
- The researchers, hence, theorized that changes in both DNA methylation status and redox conditions could influence genomic stability in BPV-1 infected cells, subsequently contributing to the pathology of sarcoids.
Significance of the Study
- This research paves the way for further understanding of the impact of BPV-1 on equine sarcoid disease.
- By identifying the connection between BPV-1 and changes in DNA methylation and oxidative stress parameters, it opens up potential avenues for targeted therapies and preventive measures.
Cite This Article
APA
Potocki L, Lewinska A, Klukowska-Rötzler J, Bugno-Poniewierska M, Koch C, Mählmann K, Janda J, Wnuk M.
(2012).
DNA hypomethylation and oxidative stress-mediated increase in genomic instability in equine sarcoid-derived fibroblasts.
Biochimie, 94(9), 2013-2024.
https://doi.org/10.1016/j.biochi.2012.05.026 Publication
Researcher Affiliations
- Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland.
MeSH Terms
- Animals
- Apoptosis
- Bovine papillomavirus 1 / physiology
- Cell Line, Tumor
- Cell Proliferation
- DNA Methylation
- Fibroblasts / metabolism
- Fibroblasts / pathology
- Fibroblasts / virology
- Genetic Predisposition to Disease
- Genomic Instability / genetics
- Horse Diseases / pathology
- Horses
- Oxidative Stress
- Ploidies
- Skin / metabolism
- Skin / pathology
- Skin / virology
- Skin Neoplasms / pathology
- Skin Neoplasms / veterinary
- Tumor Suppressor Protein p53 / metabolism
Citations
This article has been cited 7 times.- Semik-Gurgul E, Gurgul A, Szmatoła T. Transcriptome and methylome sequencing reveals altered long non-coding RNA genes expression and their aberrant DNA methylation in equine sarcoids.. Funct Integr Genomics 2023 Aug 8;23(3):268.
- Bara AW, Braszewska A, Kwasniewska J. DNA Methylation-An Epigenetic Mark in Mutagen-Treated Brachypodium distachyon Cells.. Plants (Basel) 2021 Jul 9;10(7).
- Martano M, Power K, Restucci B, Pagano I, Altamura G, Borzacchiello G, Maiolino P. Expression of vascular endothelial growth factor (VEGF) in equine sarcoid.. BMC Vet Res 2018 Sep 3;14(1):266.
- Grabowska W, Kucharewicz K, Wnuk M, Lewinska A, Suszek M, Przybylska D, Mosieniak G, Sikora E, Bielak-Zmijewska A. Curcumin induces senescence of primary human cells building the vasculature in a DNA damage and ATM-independent manner.. Age (Dordr) 2015 Feb;37(1):9744.
- Vojta A, Zoldoš V. Adaptation or malignant transformation: the two faces of epigenetically mediated response to stress.. Biomed Res Int 2013;2013:954060.
- Jintaridth P, Tungtrongchitr R, Preutthipan S, Mutirangura A. Hypomethylation of Alu elements in post-menopausal women with osteoporosis.. PLoS One 2013;8(8):e70386.
- Luzhna L, Kathiria P, Kovalchuk O. Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond.. Front Genet 2013;4:131.
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