Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells
We recently described the relationship between mitochondrial alterations and senescence as a regulatory process of cell growth in estrogen-induced pituitary tumors. In addition, it is known that this hormone promotes the DNA oxidation leading to the accumulation of mutations in mitochondrial DNA res...
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Formato: | Artículo revista |
Lenguaje: | Español |
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Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
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Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/25595 |
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Universidad Nacional de Córdoba |
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Revistas de la UNC |
language |
Español |
format |
Artículo revista |
topic |
pituitary estrogen mitochondria oxidative stress hipófisis estrógeno mitocondria estrés oxidativo |
spellingShingle |
pituitary estrogen mitochondria oxidative stress hipófisis estrógeno mitocondria estrés oxidativo Grondona , E Mongi Bragato, E Sosa, LDV Latini, A De Paul, AL Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
topic_facet |
pituitary estrogen mitochondria oxidative stress hipófisis estrógeno mitocondria estrés oxidativo |
author |
Grondona , E Mongi Bragato, E Sosa, LDV Latini, A De Paul, AL |
author_facet |
Grondona , E Mongi Bragato, E Sosa, LDV Latini, A De Paul, AL |
author_sort |
Grondona , E |
title |
Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
title_short |
Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
title_full |
Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
title_fullStr |
Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
title_full_unstemmed |
Estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
title_sort |
estrogen effects on the mitochondrial dynamic and oxidative damage response in normal and tumoral pituitary cells |
description |
We recently described the relationship between mitochondrial alterations and senescence as a regulatory process of cell growth in estrogen-induced pituitary tumors. In addition, it is known that this hormone promotes the DNA oxidation leading to the accumulation of mutations in mitochondrial DNA resulting in energy deficiencies and cellular damage with carcinogenic potential. In this context, we set out to evaluate possible 17β-estradiol (E2) pro-oxidant actions in vitro on mitochondrial dynamics and the activation of the damage response under pituitary tumor contexts.
Pituitary tumor development was induced in adult male Wistar rats by subcutaneous implantation of silastic capsules containing estradiol benzoate (30 mg) for 10 days (E10; n=5). The control group was implanted with empty capsules (n=5). Once the deadlines were met, pituitary glands were collected and cells cultured and exposed to E2 (1-10-100nM) for 15, 30 and 60 min. The reactive oxygen species (ROS) generation was analyzed by flow cytometry, the 8OHdG and p-Nrf2 co-expression, as indicators of DNA oxidation and activation of response to oxidative damage, was evaluated by immunofluorescence. Mitochondrial protein expression: MFN2 and OPA-1 (mitochondrial fusion) and p-Drp1 (mitochondrial fission) was assessed by western blot. Statistical analysis: ANOVA-Fischer (p <0.05).
In tumoral cells, physiological doses of E2 (1nM) promoted a significant increase in the ROS production after short exposure times, whereas in normal cells, 10nM E2 induced this oxidative response after 30min of treatment. Likewise, an increase in the co-expression of 8OHdG and p-Nrf2 was observed as the concentration and the time of exposure to E2 increased. This same behavior was observed in the expression of mitochondrial proteins, indicating a tendency towards fusion.
In tumoral cells, E2 would promote a pro-oxidant environment that would be counterbalanced by the activation of antioxidant pathways mediated by Nrf2. These clear evidences of oxidative stress would trigger alterations in mitochondrial dynamics, favoring the fusion process, as a measure of metabolic readaptation. These responses would guarantee cell viability allowing to meet the highest energy demands, typical of the tumor context. |
publisher |
Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
publishDate |
2019 |
url |
https://revistas.unc.edu.ar/index.php/med/article/view/25595 |
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Revistas |
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