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Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-?B activation.

ABSTRACT: 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-? 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-?B in the antiapoptotic action of HN. STAT3 inhibition reversed the inhibitory effect of HN on TNF-?-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-?B pathway did not affect action of HN on normal anterior pituitary cells but blocked the cytoprotective effect of HN on TNF-?-induced apoptosis of GH3 cells, suggesting that the NF-?B pathway is involved in HN action in tumor pituitary cells. HN also induced NF-?B-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.

SUBMITTER: Gottardo MF

PROVIDER: S-EPMC5704037 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Gottardo María Florencia MF Moreno Ayala Mariela M Ferraris Jimena J Zárate Sandra S Pisera Daniel D Candolfi Marianela M Jaita Gabriela G Seilicovich Adriana A

Journal of cell communication and signaling 20170404 4

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 an ...[more]

PMID: 28378125

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Project description:Pituitary tumors do not pose a threat to life but can cause visual disturbances and serious clinical syndromes, such as infertility and metabolic syndrome. Therefore, screening of key genes involved in the occurrence and development of pituitary tumors can provide new targets for the treatment of pituitary tumors. The aim of the present study was to investigate the molecular mechanism of long non‑coding (lnc.) RNA maternally expressed 3 (MEG3) in cell proliferation, apoptosis and epithelial‑mesenchymal transition (EMT) processes of pituitary tumor. Tissue samples were obtained from 34 patients who underwent surgical treatment of pituitary tumors. Pituitary tumor cells (GH3 and MMQ) were transfected with pcDNA3.1(+)‑MEG3, short hairpin (sh)MEG3, microRNA (miR)‑23‑3p inhibitor or their controls using Lipofectamine® 2000. Reverse transcription‑quantitative PCR and western blot analyses were used to detect the levels of MEG3, miR‑23b‑3p and FOXO4, as well as proliferation‑, apoptosis‑ and EMT‑associated genes and proteins. Cell Counting Kit‑8 and flow cytometry assays were performed to detect proliferation and apoptosis, and Transwell assay was undertaken to assess invasion and migration. Luciferase reporter and RNA pulldown assays were performed to verify the binding between lncRNA MEG3, miR‑23b‑3p and FOXO4. Pearson's correlation analysis was used to analyze the correlation between expression levels of MEG3, miR‑23b‑3p and FOXO4. lncRNA MEG3 was expressed at lower levels in pituitary tumor tissues and cells. Overexpression of lncRNA MEG3 inhibited proliferation, invasion and migration and accelerated apoptosis of pituitary tumor cells. lncRNA MEG3 negatively regulated miR‑23b‑3p expression levels, while miR‑23b‑3p negatively regulated FOXO4 expression levels. Overexpression of lncRNA MEG3 inhibited the EMT process in pituitary tumor cells. miR‑23‑3p inhibitor rescued the effect of shMEG3 on proliferation, invasion, migration, apoptosis and the EMT process in pituitary tumor cells. lncRNA MEG3 inhibited pituitary tumor development by participating in cell proliferation, apoptosis and the EMT process, which may present a novel target for pituitary tumor treatment.

Dataset Information

Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-?B activation.

Publications

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

Similar Datasets

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