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Lookup NU author(s): Dr Marco Malavolta, Ogo Ogo
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© 2017 Elsevier Inc. Endothelial cell senescence and Zn nutritional status influence cardiovascular disease. The influence of Zn appears dichotomous, hence it is imperative to understand the relationship with cellular senescence to improve knowledge about the molecular and cellular basis of the disease. Here we aimed to determine: 1) the impact of chronic exposure to a moderately high dose of Zn on senescence of endothelial cells; 2) the changes in Zn homeostasis during the lifespan of primary cultured endothelial cells; and 3) the susceptibility of proliferating and senescent endothelial cells to cell death after short term exposure to increasing doses of Zn and of the Zn chelator TPEN. Chronic exposure to Zn accelerated senescence and untreated cells at later passages, where doubling time had increased, displayed relocation of labile Zn and altered expression of genes involved in the response to Zn toxicity, including SLC30A1, SLC39A6, SLC30A5, SLC30A10 and metallothioneins, indicating that senescent cells have altered zinc homeostasis. Most Zn-dependent genes that were expressed differently between early and late passages were correlated with changes in the expression of anti-apoptotic genes. Short-term treatment with a high dose of Zn leads to cell death, but only in the population of cells at both earlier and later passages that had already entered senescence. In contrast, Zn depletion led to death of cells at earlier but not later passages, which suggests that there are sub-populations of senescent cells that are resistant to Zn depletion. This resistant senescent cell population may accumulate under conditions of Zn deficiency and contribute to vascular pathology.
Author(s): Malavolta M, Costarelli L, Giacconi R, Basso A, Piacenza F, Pierpaoli E, Provinciali M, Ogo OA, Ford D
Publication type: Article
Publication status: Published
Journal: Experimental Gerontology
Year: 2017
Volume: 99
Pages: 35-45
Print publication date: 01/12/2017
Online publication date: 14/09/2017
Acceptance date: 08/09/2017
ISSN (print): 0531-5565
ISSN (electronic): 1873-6815
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.exger.2017.09.006
DOI: 10.1016/j.exger.2017.09.006
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