The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely sen...

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Autores principales:	Ramesh Yentrapalli, Omid Azimzadeh, Arundhathi Sriharshan, Katharina Malinowsky, Juliane Merl, Andrzej Wojcik, Mats Harms-Ringdahl, Michael J Atkinson, Karl-Friedrich Becker, Siamak Haghdoost, Soile Tapio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b2dff6adb4d485785411ec1693318d6
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spelling	oai:doaj.org-article:1b2dff6adb4d485785411ec1693318d62021-11-18T09:01:43ZThe PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.1932-620310.1371/journal.pone.0070024https://doaj.org/article/1b2dff6adb4d485785411ec1693318d62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936371/?tool=EBIhttps://doaj.org/toc/1932-6203The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.Ramesh YentrapalliOmid AzimzadehArundhathi SriharshanKatharina MalinowskyJuliane MerlAndrzej WojcikMats Harms-RingdahlMichael J AtkinsonKarl-Friedrich BeckerSiamak HaghdoostSoile TapioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e70024 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ramesh Yentrapalli Omid Azimzadeh Arundhathi Sriharshan Katharina Malinowsky Juliane Merl Andrzej Wojcik Mats Harms-Ringdahl Michael J Atkinson Karl-Friedrich Becker Siamak Haghdoost Soile Tapio The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
description	The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.
format	article
author	Ramesh Yentrapalli Omid Azimzadeh Arundhathi Sriharshan Katharina Malinowsky Juliane Merl Andrzej Wojcik Mats Harms-Ringdahl Michael J Atkinson Karl-Friedrich Becker Siamak Haghdoost Soile Tapio
author_facet	Ramesh Yentrapalli Omid Azimzadeh Arundhathi Sriharshan Katharina Malinowsky Juliane Merl Andrzej Wojcik Mats Harms-Ringdahl Michael J Atkinson Karl-Friedrich Becker Siamak Haghdoost Soile Tapio
author_sort	Ramesh Yentrapalli
title	The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
title_short	The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
title_full	The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
title_fullStr	The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
title_full_unstemmed	The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
title_sort	pi3k/akt/mtor pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1b2dff6adb4d485785411ec1693318d6
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The PI3K/Akt/mTOR pathway is implicated in the premature senescence of primary human endothelial cells exposed to chronic radiation.

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