Changes in Zn homeostasis during long term culture of primary endothelial cells and effects of Zn on endothelial cell senescence
| Autor: | Ogo A. Ogo, Dianne Ford, Francesco Piacenza, L. Costarelli, Marco Malavolta, Robertina Giacconi, Elisa Pierpaoli, Mauro Provinciali, Andrea Basso |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Senescence Aging Programmed cell death Time Factors Population Primary Cell Culture Apoptosis Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Databases Genetic Genetics Human Umbilical Vein Endothelial Cells Doubling time Homeostasis Humans education Molecular Biology Gene Cell Shape Cells Cultured Cellular Senescence Cell Proliferation Chelating Agents education.field_of_study Dose-Response Relationship Drug Gene Expression Profiling Endothelial Cells Cell Biology C400 Ethylenediamines C900 Zinc Sulfate Cell biology Endothelial stem cell 030104 developmental biology Gene Expression Regulation Toxicity Immunology 030217 neurology & neurosurgery |
| Zdroj: | Experimental gerontology. 99 |
| ISSN: | 1873-6815 0531-5565 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect