Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress

In our previous study, we found that high doses of several substances with antioxidant capacities (Tempol, resveratrol, diphenyleneiodonium) can cause genotoxic stress and induce premature senescence in the human mesenchymal stem cells (MSCs). Here, using whole-transcriptome analysis, we revealed th...

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Autores principales:	Olga Lyublinskaya, Julia Kornienko, Julia Ivanova, Natalia Pugovkina, Larisa Alekseenko, Ekaterina Lyublinskaya, Irina Tyuryaeva, Irina Smirnova, Tatiana Grinchuk, Mariia Shorokhova, Anna Krasnenko, Nikolay Plotnikov, Nikolay Nikolsky
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cell senescence stress-induced senescence antioxidants mesenchymal stem cells reductive stress endoplasmic reticulum stress Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2bb5b475aa274a41ac824af60f4f5b86
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spelling	oai:doaj.org-article:2bb5b475aa274a41ac824af60f4f5b862021-11-11T17:16:42ZInduction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress10.3390/ijms2221118511422-00671661-6596https://doaj.org/article/2bb5b475aa274a41ac824af60f4f5b862021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11851https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067In our previous study, we found that high doses of several substances with antioxidant capacities (Tempol, resveratrol, diphenyleneiodonium) can cause genotoxic stress and induce premature senescence in the human mesenchymal stem cells (MSCs). Here, using whole-transcriptome analysis, we revealed the signs of endoplasmic reticulum stress and unfolded protein response (UPR) in MSCs stressed with Tempol and resveratrol. In addition, we found the upregulation of genes, coding the UPR downstream target APC/C, and E3 ubiquitin ligase that regulate the stability of cell cycle proteins. We performed the molecular analysis, which further confirmed the untimely degradation of APC/C targets (cyclin A, geminin, and Emi1) in MSCs treated with antioxidants. Human fibroblasts responded to antioxidant applications similarly. We conclude that endoplasmic reticulum stress and impaired DNA synthesis regulation can be considered as potential triggers of cell damage and premature senescence stimulated by high-dose antioxidant treatments.Olga LyublinskayaJulia KornienkoJulia IvanovaNatalia PugovkinaLarisa AlekseenkoEkaterina LyublinskayaIrina TyuryaevaIrina SmirnovaTatiana GrinchukMariia ShorokhovaAnna KrasnenkoNikolay PlotnikovNikolay NikolskyMDPI AGarticlecell senescencestress-induced senescenceantioxidantsmesenchymal stem cellsreductive stressendoplasmic reticulum stressBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11851, p 11851 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell senescence stress-induced senescence antioxidants mesenchymal stem cells reductive stress endoplasmic reticulum stress Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	cell senescence stress-induced senescence antioxidants mesenchymal stem cells reductive stress endoplasmic reticulum stress Biology (General) QH301-705.5 Chemistry QD1-999 Olga Lyublinskaya Julia Kornienko Julia Ivanova Natalia Pugovkina Larisa Alekseenko Ekaterina Lyublinskaya Irina Tyuryaeva Irina Smirnova Tatiana Grinchuk Mariia Shorokhova Anna Krasnenko Nikolay Plotnikov Nikolay Nikolsky Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
description	In our previous study, we found that high doses of several substances with antioxidant capacities (Tempol, resveratrol, diphenyleneiodonium) can cause genotoxic stress and induce premature senescence in the human mesenchymal stem cells (MSCs). Here, using whole-transcriptome analysis, we revealed the signs of endoplasmic reticulum stress and unfolded protein response (UPR) in MSCs stressed with Tempol and resveratrol. In addition, we found the upregulation of genes, coding the UPR downstream target APC/C, and E3 ubiquitin ligase that regulate the stability of cell cycle proteins. We performed the molecular analysis, which further confirmed the untimely degradation of APC/C targets (cyclin A, geminin, and Emi1) in MSCs treated with antioxidants. Human fibroblasts responded to antioxidant applications similarly. We conclude that endoplasmic reticulum stress and impaired DNA synthesis regulation can be considered as potential triggers of cell damage and premature senescence stimulated by high-dose antioxidant treatments.
format	article
author	Olga Lyublinskaya Julia Kornienko Julia Ivanova Natalia Pugovkina Larisa Alekseenko Ekaterina Lyublinskaya Irina Tyuryaeva Irina Smirnova Tatiana Grinchuk Mariia Shorokhova Anna Krasnenko Nikolay Plotnikov Nikolay Nikolsky
author_facet	Olga Lyublinskaya Julia Kornienko Julia Ivanova Natalia Pugovkina Larisa Alekseenko Ekaterina Lyublinskaya Irina Tyuryaeva Irina Smirnova Tatiana Grinchuk Mariia Shorokhova Anna Krasnenko Nikolay Plotnikov Nikolay Nikolsky
author_sort	Olga Lyublinskaya
title	Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
title_short	Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
title_full	Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
title_fullStr	Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
title_full_unstemmed	Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress
title_sort	induction of premature cell senescence stimulated by high doses of antioxidants is mediated by endoplasmic reticulum stress
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2bb5b475aa274a41ac824af60f4f5b86
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Induction of Premature Cell Senescence Stimulated by High Doses of Antioxidants Is Mediated by Endoplasmic Reticulum Stress

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