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Open AccessArticle

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

by Tomer Harpaz 1,†, Heba Abumock 1,†, Einat Beery 1, Yonatan Edel 2,3, Meir Lahav 1,2,4, Uri Rozovski 1,2,4 and Orit Uziel 1,2,*
The Felsenstein Medical Research Center, Rabin Medical Center, Petah-Tikva 49100, Israel
Sackler School of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel
Medicine C, Rabin Medical Center, Petah-Tikva 49100, Israel
Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva 49100, Israel
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2018, 7(10), 169;
Received: 22 August 2018 / Revised: 7 October 2018 / Accepted: 8 October 2018 / Published: 15 October 2018
(This article belongs to the Special Issue The Role of Telomere Biology in Aging and Human Disease)
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.” View Full-Text
Keywords: telomeres; ethanol; shelterin; telomerase; acetaldehyde telomeres; ethanol; shelterin; telomerase; acetaldehyde
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Harpaz, T.; Abumock, H.; Beery, E.; Edel, Y.; Lahav, M.; Rozovski, U.; Uziel, O. The Effect of Ethanol on Telomere Dynamics and Regulation in Human Cells. Cells 2018, 7, 169.

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