Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset

We recently reported that the inability of osteoarthritic (OA) chondrocytes to repair oxidative stress (OS) induced DNA damage is linked to Cav-1 overexpression/improper localization. We speculated that the senescent status of OA cells was responsible for this Cav-1 dysregulation. Here, to further i...

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Autores principales:	Andreas Goutas, Zozo Outskouni, Ioanna Papathanasiou, Maria Satra, George Koliakos, Varvara Trachana
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	caveolin-1 mesenchymal stem cells oxidative stress senescence DNA damage Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8aa594b208f24b52bcfe964cc8eac60f
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spelling	oai:doaj.org-article:8aa594b208f24b52bcfe964cc8eac60f2021-11-25T17:09:23ZDysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset10.3390/cells101129392073-4409https://doaj.org/article/8aa594b208f24b52bcfe964cc8eac60f2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2939https://doaj.org/toc/2073-4409We recently reported that the inability of osteoarthritic (OA) chondrocytes to repair oxidative stress (OS) induced DNA damage is linked to Cav-1 overexpression/improper localization. We speculated that the senescent status of OA cells was responsible for this Cav-1 dysregulation. Here, to further investigate this hypothesis, we used Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) and investigated Cav-1 function as cells reached replicative senescence or upon stress induced senescence (SIPS). We showed that Cav-1 is upregulated, phosphorylated and translocated to the nucleus in young WJ-MSCs upon acute exogenous OS, and that it returns back to basal/nonphosphorylated levels and exports the nucleus in the recovery phase. However, as cells reach senescence, this regulation is lost. OS did not induce any Cav-1-mediated response, which is concomitant with the inability of older cells to restore DNA damage. Furthermore, downregulation of Cav-1 resulted in persistent OS-induced DNA damage and subsequent onset of senescence. We also report that the establishment of senescence is mediated by autophagy stimulation, since downregulation of autophagy key molecule Atg5, simultaneously with Cav-1 downregulation, was found to inhibit SIPS. Basically, we propose that Cav-1 involvement in DNA damage response can lead to senescence, either because the damage is extensive or because Cav-1 is absent/unable to perform its homeostatic role.Andreas GoutasZozo OutskouniIoanna PapathanasiouMaria SatraGeorge KoliakosVarvara TrachanaMDPI AGarticlecaveolin-1mesenchymal stem cellsoxidative stresssenescenceDNA damageBiology (General)QH301-705.5ENCells, Vol 10, Iss 2939, p 2939 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	caveolin-1 mesenchymal stem cells oxidative stress senescence DNA damage Biology (General) QH301-705.5
spellingShingle	caveolin-1 mesenchymal stem cells oxidative stress senescence DNA damage Biology (General) QH301-705.5 Andreas Goutas Zozo Outskouni Ioanna Papathanasiou Maria Satra George Koliakos Varvara Trachana Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
description	We recently reported that the inability of osteoarthritic (OA) chondrocytes to repair oxidative stress (OS) induced DNA damage is linked to Cav-1 overexpression/improper localization. We speculated that the senescent status of OA cells was responsible for this Cav-1 dysregulation. Here, to further investigate this hypothesis, we used Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) and investigated Cav-1 function as cells reached replicative senescence or upon stress induced senescence (SIPS). We showed that Cav-1 is upregulated, phosphorylated and translocated to the nucleus in young WJ-MSCs upon acute exogenous OS, and that it returns back to basal/nonphosphorylated levels and exports the nucleus in the recovery phase. However, as cells reach senescence, this regulation is lost. OS did not induce any Cav-1-mediated response, which is concomitant with the inability of older cells to restore DNA damage. Furthermore, downregulation of Cav-1 resulted in persistent OS-induced DNA damage and subsequent onset of senescence. We also report that the establishment of senescence is mediated by autophagy stimulation, since downregulation of autophagy key molecule Atg5, simultaneously with Cav-1 downregulation, was found to inhibit SIPS. Basically, we propose that Cav-1 involvement in DNA damage response can lead to senescence, either because the damage is extensive or because Cav-1 is absent/unable to perform its homeostatic role.
format	article
author	Andreas Goutas Zozo Outskouni Ioanna Papathanasiou Maria Satra George Koliakos Varvara Trachana
author_facet	Andreas Goutas Zozo Outskouni Ioanna Papathanasiou Maria Satra George Koliakos Varvara Trachana
author_sort	Andreas Goutas
title	Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
title_short	Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
title_full	Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
title_fullStr	Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
title_full_unstemmed	Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset
title_sort	dysregulation of caveolin-1 phosphorylation and nuclear translocation is associated with senescence onset
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8aa594b208f24b52bcfe964cc8eac60f
work_keys_str_mv	AT andreasgoutas dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset AT zozooutskouni dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset AT ioannapapathanasiou dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset AT mariasatra dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset AT georgekoliakos dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset AT varvaratrachana dysregulationofcaveolin1phosphorylationandnucleartranslocationisassociatedwithsenescenceonset
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Dysregulation of Caveolin-1 Phosphorylation and Nuclear Translocation Is Associated with Senescence Onset

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