http://purl.uniprot.org/citations/24022164 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/24022164 | http://www.w3.org/2000/01/rdf-schema#comment | "Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic cytokine that plays a crucial role in regulating the proliferation, differentiation, and survival of hematopoietic cells. Recent studies have shown that GM-CSF also has anti-apoptotic effects and regulates the expression of anti-apoptotic genes including Bcl-2 family proteins in neuronal cells in vitro and in vivo. However, the mechanism underlying the anti-apoptotic function of GM-CSF is not well understood. In the present work, we examined the role of phosphoinositide 3-kinase (PI3K)-AKT signal pathway in the anti-apoptotic activity of GM-CSF in mouse neural progenitor cells (NPCs). In terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, the anti-apoptotic effect of GM-CSF (apoptotic population of approximately 8.17 %) on staurosporine-induced apoptosis of NPCs (31.09 %) was significantly blocked by LY294002, an inhibitor of PI3K signal (24.04 %). We found that the PI3K-AKT signal pathway induced by GM-CSF treatment activated nuclear factor κB (NF-κB) and increased the expression of hypoxia-inducible factor 1α (HIF-1α) in normoxic conditions. Analyses using specific small interfering RNAs (siRNAs) showed that NF-κB was an upstream molecule of HIF-1α and activated its expression at the mRNA level. Further analyses using the siRNAs and chromatin immunoprecipitation (ChIP) showed that HIF-1α was responsible for the induced expression of survivin, a member of the inhibitor of apoptosis proteins (IAPs). Each of the specific siRNAs for NF-κB, HIF-1α, and survivin inhibited significantly the anti-apoptotic activity of GM-CSF on the staurosporine-induced apoptosis in NPCs in TUNEL assays. The results of this study showed the downstream signals and mechanism of PI3K/AKT-mediated anti-apoptotic activity of GM-CSF in NPCs, particularly revealing the role of the NF-κB-HIF-1α-survivin cascade."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.org/dc/terms/identifier | "doi:10.1007/s12035-013-8550-3"xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/author | "Choi J.K."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/author | "Kim K.H."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/author | "Choi B.H."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/author | "Park S.R."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/name | "Mol Neurobiol"xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/pages | "724-733"xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/title | "Granulocyte macrophage colony-stimulating factor shows anti-apoptotic activity via the PI3K-NF-kappaB-HIF-1alpha-survivin pathway in mouse neural progenitor cells."xsd:string |
http://purl.uniprot.org/citations/24022164 | http://purl.uniprot.org/core/volume | "49"xsd:string |
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