AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival

Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Basic fibroblast growth factor is essential for PSC survival, stemness and self-renewal. PI3K/AKT pathway regulates cell viability and apop...

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Publicado:	2016
Materias:	glycogen synthase kinase 3beta oncoprotein cell culture cell survival gene expression regulation human metabolism physiology pluripotent stem cell signal transduction Cell Survival Cells, Cultured Gene Expression Regulation Glycogen Synthase Kinase 3 beta Humans Oncogene Protein v-akt Pluripotent Stem Cells Signal Transduction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v6_n_p_Romorini http://hdl.handle.net/20.500.12110/paper_20452322_v6_n_p_Romorini
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_20452322_v6_n_p_Romorini
record_format	dspace
spelling	paper:paper_20452322_v6_n_p_Romorini2023-06-08T16:33:27Z AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival glycogen synthase kinase 3beta oncoprotein cell culture cell survival gene expression regulation human metabolism physiology pluripotent stem cell signal transduction Cell Survival Cells, Cultured Gene Expression Regulation Glycogen Synthase Kinase 3 beta Humans Oncogene Protein v-akt Pluripotent Stem Cells Signal Transduction Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Basic fibroblast growth factor is essential for PSC survival, stemness and self-renewal. PI3K/AKT pathway regulates cell viability and apoptosis in many cell types. Although it has been demonstrated that PI3K/AKT activation by bFGF is relevant for PSC stemness maintenance its role on PSC survival remains elusive. In this study we explored the molecular mechanisms involved in the regulation of PSC survival by AKT. We found that inhibition of AKT with three non-structurally related inhibitors (GSK690693, AKT inhibitor VIII and AKT inhibitor IV) decreased cell viability and induced apoptosis. We observed a rapid increase in phosphatidylserine translocation and in the extent of DNA fragmentation after inhibitors addition. Moreover, abrogation of AKT activity led to Caspase-9, Caspase-3, and PARP cleavage. Importantly, we demonstrated by pharmacological inhibition and siRNA knockdown that GSK3β signaling is responsible, at least in part, of the apoptosis triggered by AKT inhibition. Moreover, GSK3β inhibition decreases basal apoptosis rate and promotes PSC proliferation. In conclusion, we demonstrated that AKT activation prevents apoptosis, partly through inhibition of GSK3β, and thus results relevant for PSC survival. © 2016 The Author(s). 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v6_n_p_Romorini http://hdl.handle.net/20.500.12110/paper_20452322_v6_n_p_Romorini
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	glycogen synthase kinase 3beta oncoprotein cell culture cell survival gene expression regulation human metabolism physiology pluripotent stem cell signal transduction Cell Survival Cells, Cultured Gene Expression Regulation Glycogen Synthase Kinase 3 beta Humans Oncogene Protein v-akt Pluripotent Stem Cells Signal Transduction
spellingShingle	glycogen synthase kinase 3beta oncoprotein cell culture cell survival gene expression regulation human metabolism physiology pluripotent stem cell signal transduction Cell Survival Cells, Cultured Gene Expression Regulation Glycogen Synthase Kinase 3 beta Humans Oncogene Protein v-akt Pluripotent Stem Cells Signal Transduction AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
topic_facet	glycogen synthase kinase 3beta oncoprotein cell culture cell survival gene expression regulation human metabolism physiology pluripotent stem cell signal transduction Cell Survival Cells, Cultured Gene Expression Regulation Glycogen Synthase Kinase 3 beta Humans Oncogene Protein v-akt Pluripotent Stem Cells Signal Transduction
description	Human embryonic and induced pluripotent stem cells are self-renewing pluripotent stem cells (PSC) that can differentiate into a wide range of specialized cells. Basic fibroblast growth factor is essential for PSC survival, stemness and self-renewal. PI3K/AKT pathway regulates cell viability and apoptosis in many cell types. Although it has been demonstrated that PI3K/AKT activation by bFGF is relevant for PSC stemness maintenance its role on PSC survival remains elusive. In this study we explored the molecular mechanisms involved in the regulation of PSC survival by AKT. We found that inhibition of AKT with three non-structurally related inhibitors (GSK690693, AKT inhibitor VIII and AKT inhibitor IV) decreased cell viability and induced apoptosis. We observed a rapid increase in phosphatidylserine translocation and in the extent of DNA fragmentation after inhibitors addition. Moreover, abrogation of AKT activity led to Caspase-9, Caspase-3, and PARP cleavage. Importantly, we demonstrated by pharmacological inhibition and siRNA knockdown that GSK3β signaling is responsible, at least in part, of the apoptosis triggered by AKT inhibition. Moreover, GSK3β inhibition decreases basal apoptosis rate and promotes PSC proliferation. In conclusion, we demonstrated that AKT activation prevents apoptosis, partly through inhibition of GSK3β, and thus results relevant for PSC survival. © 2016 The Author(s).
title	AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
title_short	AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
title_full	AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
title_fullStr	AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
title_full_unstemmed	AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival
title_sort	akt/gsk3β signaling pathway is critically involved in human pluripotent stem cell survival
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20452322_v6_n_p_Romorini http://hdl.handle.net/20.500.12110/paper_20452322_v6_n_p_Romorini
_version_	1768541725576396800

AKT/GSK3β signaling pathway is critically involved in human pluripotent stem cell survival

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