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The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells

Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. Ho...

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Autores principales: Harpaz, Tomer, Abumock, Heba, Beery, Einat, Edel, Yonatan, Lahav, Meir, Rozovski, Uri, Uziel, Orit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210749/
https://www.ncbi.nlm.nih.gov/pubmed/30326633
http://dx.doi.org/10.3390/cells7100169
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author Harpaz, Tomer
Abumock, Heba
Beery, Einat
Edel, Yonatan
Lahav, Meir
Rozovski, Uri
Uziel, Orit
author_facet Harpaz, Tomer
Abumock, Heba
Beery, Einat
Edel, Yonatan
Lahav, Meir
Rozovski, Uri
Uziel, Orit
author_sort Harpaz, Tomer
collection PubMed
description Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. However, the causal relationship between stress and TL length and the molecular mechanisms underlying that relationship are far from being understood. This study describes the effect of moderate concentrations of ethanol, equivalent to social drinking, on human TL dynamics and partially elucidates the mechanism mediating this effect. The exposure of Immortalized human foreskin fibroblast, primary human foreskin fibroblast and human hepatocellular carcinoma cells to 25 mM ethanol for one week moderately shortened telomeres in all cells. Similar TL shortening was obtained following cells’ exposure to 25 µM acetaldehyde (AcH) and to a much lower extent after exposure to 4-methylpyrazolean, an inhibitor of alcoholdehydrogenase, suggesting that AcH plays a key role in ethanol-dependent telomere shortening. Telomerase activity was not involved in this effect. TRF2 and several TRF2 binding proteins increased their binding to TLs after ethanol treatment, implying their involvement in this effect. The methylation status of several sub-telomeric regions increased in response to EtOH exposure. Gene expression profiling showed distinct patterns in cells treated with EtOH and in cells recovered from EtOH. In addition to cellular ageing, the described telomere shortening may contribute to the carcinogenic potential of acute alcohol consumption; both are associated with the shortening of TLs and provide new insights regarding the moderate consumption of alcohol referred to as “social drinking.”
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spelling pubmed-62107492018-11-02 The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells Harpaz, Tomer Abumock, Heba Beery, Einat Edel, Yonatan Lahav, Meir Rozovski, Uri Uziel, Orit Cells Article Telomeres (TLs) protect chromosome ends from chromosomal fusion and degradation, thus conferring genomic stability, and play crucial roles in cellular aging and disease. Recent studies have found a correlation between environmental, physiological and even mental stresses on TL dynamics in humans. However, the causal relationship between stress and TL length and the molecular mechanisms underlying that relationship are far from being understood. This study describes the effect of moderate concentrations of ethanol, equivalent to social drinking, on human TL dynamics and partially elucidates the mechanism mediating this effect. The exposure of Immortalized human foreskin fibroblast, primary human foreskin fibroblast and human hepatocellular carcinoma cells to 25 mM ethanol for one week moderately shortened telomeres in all cells. Similar TL shortening was obtained following cells’ exposure to 25 µM acetaldehyde (AcH) and to a much lower extent after exposure to 4-methylpyrazolean, an inhibitor of alcoholdehydrogenase, suggesting that AcH plays a key role in ethanol-dependent telomere shortening. Telomerase activity was not involved in this effect. TRF2 and several TRF2 binding proteins increased their binding to TLs after ethanol treatment, implying their involvement in this effect. The methylation status of several sub-telomeric regions increased in response to EtOH exposure. Gene expression profiling showed distinct patterns in cells treated with EtOH and in cells recovered from EtOH. In addition to cellular ageing, the described telomere shortening may contribute to the carcinogenic potential of acute alcohol consumption; both are associated with the shortening of TLs and provide new insights regarding the moderate consumption of alcohol referred to as “social drinking.” MDPI 2018-10-15 /pmc/articles/PMC6210749/ /pubmed/30326633 http://dx.doi.org/10.3390/cells7100169 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Harpaz, Tomer
Abumock, Heba
Beery, Einat
Edel, Yonatan
Lahav, Meir
Rozovski, Uri
Uziel, Orit
The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title_full The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title_fullStr The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title_full_unstemmed The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title_short The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells
title_sort effect of ethanol on telomere dynamics and regulation in human cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210749/
https://www.ncbi.nlm.nih.gov/pubmed/30326633
http://dx.doi.org/10.3390/cells7100169
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