Leptin protects placental cells from apoptosis induced by acidic stress

Development of the human placenta is critical for a successful pregnancy. The placenta allows the exchange of oxygen and carbon dioxide and is crucial to manage acid-base balance within a narrow pH. It is known that low pH levels are a risk of apoptosis in several tissues. However, there has been li...

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Guardado en:
Detalles Bibliográficos
Publicado: 2019
Materias:
Acidic stress
Apoptosis
Leptin
Placenta
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0302766X_v375_n3_p733_PerezPerez
http://hdl.handle.net/20.500.12110/paper_0302766X_v375_n3_p733_PerezPerez
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paper:paper_0302766X_v375_n3_p733_PerezPerez
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spelling paper:paper_0302766X_v375_n3_p733_PerezPerez2023-06-08T15:28:11Z Leptin protects placental cells from apoptosis induced by acidic stress Acidic stress Apoptosis Leptin Placenta Development of the human placenta is critical for a successful pregnancy. The placenta allows the exchange of oxygen and carbon dioxide and is crucial to manage acid-base balance within a narrow pH. It is known that low pH levels are a risk of apoptosis in several tissues. However, there has been little discussion about the effect of acidic stress in the placenta. Leptin is produced by the placenta with a trophic autocrine effect. Previous results of our group have demonstrated that leptin prevents apoptosis of trophoblast cells under different stress conditions such as serum deprivation and hyperthermia. The purpose of the present work is to evaluate acidic stress consequences in trophoblast explant survival and to determine leptin action in these conditions. For this objective, term human trophoblast explants were cultured at physiological pH (pH 7.4) and at acidic pH (pH 6.8) in the presence or absence of leptin. Western blot assays were performed to study the abundance of active caspase-3 and the p89 fragment of PARP-1. Pro-apoptotic and pro-survival members of Bcl-2 family, as Bax, t-Bid, and Bcl-2, were studied. Moreover, p53 pathway was also evaluated including Mdm-2, the main p53 regulator. Active caspase-3 and cleaved PARP-1 abundances were increased at low extracellular pH. Moreover, t-Bid levels were also augmented as well as p53 expression and phosphorylation on S46. Leptin treatment prevents the consequences of acidosis, decreasing p53 expression and increasing Mdm-2 expression. In summary, this work demonstrated for first time that low pH induces apoptosis of human trophoblast explants involving apoptotic intrinsic pathway, and leptin impairs this effect. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature. 2019 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0302766X_v375_n3_p733_PerezPerez http://hdl.handle.net/20.500.12110/paper_0302766X_v375_n3_p733_PerezPerez
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Acidic stress
Apoptosis
Leptin
Placenta
spellingShingle Acidic stress
Apoptosis
Leptin
Placenta
Leptin protects placental cells from apoptosis induced by acidic stress
topic_facet Acidic stress
Apoptosis
Leptin
Placenta
description Development of the human placenta is critical for a successful pregnancy. The placenta allows the exchange of oxygen and carbon dioxide and is crucial to manage acid-base balance within a narrow pH. It is known that low pH levels are a risk of apoptosis in several tissues. However, there has been little discussion about the effect of acidic stress in the placenta. Leptin is produced by the placenta with a trophic autocrine effect. Previous results of our group have demonstrated that leptin prevents apoptosis of trophoblast cells under different stress conditions such as serum deprivation and hyperthermia. The purpose of the present work is to evaluate acidic stress consequences in trophoblast explant survival and to determine leptin action in these conditions. For this objective, term human trophoblast explants were cultured at physiological pH (pH 7.4) and at acidic pH (pH 6.8) in the presence or absence of leptin. Western blot assays were performed to study the abundance of active caspase-3 and the p89 fragment of PARP-1. Pro-apoptotic and pro-survival members of Bcl-2 family, as Bax, t-Bid, and Bcl-2, were studied. Moreover, p53 pathway was also evaluated including Mdm-2, the main p53 regulator. Active caspase-3 and cleaved PARP-1 abundances were increased at low extracellular pH. Moreover, t-Bid levels were also augmented as well as p53 expression and phosphorylation on S46. Leptin treatment prevents the consequences of acidosis, decreasing p53 expression and increasing Mdm-2 expression. In summary, this work demonstrated for first time that low pH induces apoptosis of human trophoblast explants involving apoptotic intrinsic pathway, and leptin impairs this effect. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
title Leptin protects placental cells from apoptosis induced by acidic stress
title_short Leptin protects placental cells from apoptosis induced by acidic stress
title_full Leptin protects placental cells from apoptosis induced by acidic stress
title_fullStr Leptin protects placental cells from apoptosis induced by acidic stress
title_full_unstemmed Leptin protects placental cells from apoptosis induced by acidic stress
title_sort leptin protects placental cells from apoptosis induced by acidic stress
publishDate 2019
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0302766X_v375_n3_p733_PerezPerez
http://hdl.handle.net/20.500.12110/paper_0302766X_v375_n3_p733_PerezPerez
_version_ 1768542987127619584

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