PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection

PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection

Emerging strategies that center upon the mammalian target of rapamycin (mTOR) signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO), a novel agent for nervous system disorders, prevents apoptotic SH-...

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Main Authors: Chong, Zhao Zhong, Shang, Yan Chen, Wang, Shaohui, Maiese, Kenneth
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445503/
id pubmed-3445503
recordtype oai_dc
spelling pubmed-34455032012-10-01 PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection Chong, Zhao Zhong Shang, Yan Chen Wang, Shaohui Maiese, Kenneth Research Article Emerging strategies that center upon the mammalian target of rapamycin (mTOR) signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO), a novel agent for nervous system disorders, prevents apoptotic SH-SY5Y cell injury in an oxidative stress model of oxygen-glucose deprivation through phosphatidylinositol-3-kinase (PI 3-K)/protein kinase B (Akt) dependent activation of mTOR signaling and phosphorylation of the downstream pathways of p70 ribosomal S6 kinase (p70S6K), eukaryotic initiation factor 4E-binding protein 1 (4EBP1), and proline rich Akt substrate 40 kDa (PRAS40). PRAS40 is an important regulatory component either alone or in conjunction with EPO signal transduction that can determine cell survival through apoptotic caspase 3 activation. EPO and the PI 3-K/Akt pathways control cell survival and mTOR activity through the inhibitory post-translational phosphorylation of PRAS40 that leads to subcellular binding of PRAS40 to the cytoplasmic docking protein 14-3-3. However, modulation and phosphorylation of PRAS40 is independent of other protective pathways of EPO that involve extracellular signal related kinase (ERK 1/2) and signal transducer and activator of transcription (STAT5). Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise. Public Library of Science 2012-09-18 /pmc/articles/PMC3445503/ /pubmed/23029019 http://dx.doi.org/10.1371/journal.pone.0045456 Text en © 2012 Chong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chong, Zhao Zhong
Shang, Yan Chen
Wang, Shaohui
Maiese, Kenneth
spellingShingle Chong, Zhao Zhong
Shang, Yan Chen
Wang, Shaohui
Maiese, Kenneth
PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
author_facet Chong, Zhao Zhong
Shang, Yan Chen
Wang, Shaohui
Maiese, Kenneth
author_sort Chong, Zhao Zhong
title PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
title_short PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
title_full PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
title_fullStr PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
title_full_unstemmed PRAS40 Is an Integral Regulatory Component of Erythropoietin mTOR Signaling and Cytoprotection
title_sort pras40 is an integral regulatory component of erythropoietin mtor signaling and cytoprotection
description Emerging strategies that center upon the mammalian target of rapamycin (mTOR) signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO), a novel agent for nervous system disorders, prevents apoptotic SH-SY5Y cell injury in an oxidative stress model of oxygen-glucose deprivation through phosphatidylinositol-3-kinase (PI 3-K)/protein kinase B (Akt) dependent activation of mTOR signaling and phosphorylation of the downstream pathways of p70 ribosomal S6 kinase (p70S6K), eukaryotic initiation factor 4E-binding protein 1 (4EBP1), and proline rich Akt substrate 40 kDa (PRAS40). PRAS40 is an important regulatory component either alone or in conjunction with EPO signal transduction that can determine cell survival through apoptotic caspase 3 activation. EPO and the PI 3-K/Akt pathways control cell survival and mTOR activity through the inhibitory post-translational phosphorylation of PRAS40 that leads to subcellular binding of PRAS40 to the cytoplasmic docking protein 14-3-3. However, modulation and phosphorylation of PRAS40 is independent of other protective pathways of EPO that involve extracellular signal related kinase (ERK 1/2) and signal transducer and activator of transcription (STAT5). Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445503/
_version_ 1611909823171919872

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