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Artículo

Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-κB activation

Gottardo, María FlorenciaIcon ; Moreno Ayala, Mariela AlejandraIcon ; Ferraris, Maria JimenaIcon ; Zarate, Sandra CristinaIcon ; Pisera, Daniel AlbertoIcon ; Candolfi, MarianelaIcon ; Jaita, Gabriela AlejandraIcon ; Seilicovich, AdrianaIcon
Fecha de publicación: 12/2017
Editorial: Springer Netherlands
Revista: Journal of Cell Communication and Signaling
ISSN: 1873-9601
e-ISSN: 1873-961X
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Fisiología

Resumen

Humanin (HN) and Rattin (HNr), its homologous in the rat, are peptides with cytoprotective action in several cell types such as neurons, lymphocytes and testicular germ cells. Previously, we have shown that HNr is expressed in pituitary cells and that HN inhibited the apoptotic effect of TNF-α in both normal and tumor pituitary cells. The aim of the present study was to identify signaling pathways that mediate the antiapoptotic effect of HN in anterior pituitary cells from ovariectomized rats and in GH3 cells, a somatolactotrope cell line. We assessed the role of STAT3, JNK, Akt and MAPKs as well as proteins of the Bcl-2 family, previously implicated in the antiapoptotic effect of HN. We also evaluated the participation of NF-κB in the antiapoptotic action of HN. STAT3 inhibition reversed the inhibitory effect of HN on TNF-α-induced apoptosis in normal and pituitary tumor cells, indicating that STAT3 signaling pathway mediates the antiapoptotic effect of HN on pituitary cells. Inhibition of NF-κB pathway did not affect action of HN on normal anterior pituitary cells but blocked the cytoprotective effect of HN on TNF-α-induced apoptosis of GH3 cells, suggesting that the NF-κB pathway is involved in HN action in tumor pituitary cells. HN also induced NF-κB-p65 nuclear translocation in these cells. In pituitary tumor cells, JNK and MEK inhibitors also impaired HN cytoprotective action. In addition, HN increased Bcl-2 expression and decreased Bax mitochondrial translocation. Since HN expression in GH3 cells is higher than in normal pituitary cells, we may suggest that through multiple pathways HN could be involved in pituitary tumorigenesis.
Palabras clave: APOPTOSIS , BCL-2 FAMILY PROTEINS , HUMANIN , NF-ΚB , PITUITARY , STAT3
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/91534
URL: https://link.springer.com/article/10.1007%2Fs12079-017-0388-4
DOI: http://dx.doi.org/10.1007/s12079-017-0388-4
Colecciones
Articulos(BIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Articulos(INBIOMED)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Citación
Gottardo, María Florencia; Moreno Ayala, Mariela Alejandra; Ferraris, Maria Jimena; Zarate, Sandra Cristina; Pisera, Daniel Alberto; et al.; Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-κB activation; Springer Netherlands; Journal of Cell Communication and Signaling; 11; 4; 12-2017; 329-340
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