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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Grondona , E, Mongi Bragato, E, Sosa, LDV, Latini, A, De Paul, AL
Formato: Artículo revista
Lenguaje:Español
Publicado: Universidad Nacional Cba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019
Materias:
Acceso en línea:https://revistas.unc.edu.ar/index.php/med/article/view/25595
Aporte de:
id I10-R10article-25595
record_format ojs
institution Universidad Nacional de Córdoba
institution_str I-10
repository_str R-10
container_title_str 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
work_keys_str_mv AT grondonae estrogeneffectsonthemitochondrialdynamicandoxidativedamageresponseinnormalandtumoralpituitarycells
AT mongibragatoe estrogeneffectsonthemitochondrialdynamicandoxidativedamageresponseinnormalandtumoralpituitarycells
AT sosaldv estrogeneffectsonthemitochondrialdynamicandoxidativedamageresponseinnormalandtumoralpituitarycells
AT latinia estrogeneffectsonthemitochondrialdynamicandoxidativedamageresponseinnormalandtumoralpituitarycells
AT depaulal estrogeneffectsonthemitochondrialdynamicandoxidativedamageresponseinnormalandtumoralpituitarycells
AT grondonae efectosdelestrogenosobreladinamicamitocondrialylarespuestaaldanooxidativoencelulashipofisariasnormalesytumorales
AT mongibragatoe efectosdelestrogenosobreladinamicamitocondrialylarespuestaaldanooxidativoencelulashipofisariasnormalesytumorales
AT sosaldv efectosdelestrogenosobreladinamicamitocondrialylarespuestaaldanooxidativoencelulashipofisariasnormalesytumorales
AT latinia efectosdelestrogenosobreladinamicamitocondrialylarespuestaaldanooxidativoencelulashipofisariasnormalesytumorales
AT depaulal efectosdelestrogenosobreladinamicamitocondrialylarespuestaaldanooxidativoencelulashipofisariasnormalesytumorales
bdutipo_str Revistas
_version_ 1764819782322880513