Cited 106 times in
Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to follicle-stimulating hormone
DC Field | Value | Language |
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dc.contributor.author | 이은직 | - |
dc.date.accessioned | 2015-04-24T16:34:30Z | - |
dc.date.available | 2015-04-24T16:34:30Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0013-7227 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/103770 | - |
dc.description.abstract | FSH stimulation of granulosa cells (GCs) results in increased hypoxia-inducible factor (HIF)-1alpha protein levels and HIF-1 activity that is necessary for up-regulation of certain FSH target genes including vascular endothelial growth factor. We report that the role of the phosphatidylinositol (PI)-3-kinase/AKT pathway in increasing HIF-1alpha protein in FSH-stimulated GCs extends beyond an increase in mammalian target of rapamycin-stimulated translation. FSH increases phosphorylation of the AKT target mouse double-minute 2 (MDM2); a phosphomimetic mutation of MDM2 is sufficient to induce HIF-1 activity. The PI3-kinase/AKT target forkhead box-containing protein O subfamily 1 (FOXO1) also effects the accumulation of HIF-1alpha as evidenced by the ability of a constitutively active FOXO1 mutant to inhibit the induction by FSH of HIF-1alpha protein and HIF-1 activity. Activation of the PI3-kinase/AKT pathway in GCs by IGF-I is sufficient to induce HIF-1alpha protein but surprisingly not HIF-1 activity. HIF-1 activity also appears to require a PD98059-sensitive protein (kinase) activity stimulated by FSH that is both distinct from mitogen-activated ERK kinase1/2 or 5 and independent of the PI3-kinase/AKT pathway. These results indicate that FSH-stimulated HIF-1 activation leading to up-regulation of targets such as vascular endothelial growth factor requires not only PI3-kinase/AKT-mediated activation of mammalian target of rapamycin as well as phosphorylation of FOXO1 and possibly MDM2 but also a protein (kinase) activity that is inhibited by the classic ERK kinase inhibitor PD98059 but not ERK1/2 or 5. Thus, regulation of HIF-1 activity in GCs by FSH under normoxic conditions is complex and requires input from multiple signaling pathways. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 915~928 | - |
dc.relation.isPartOf | ENDOCRINOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/physiology* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Follicle Stimulating Hormone/pharmacology* | - |
dc.subject.MESH | Forkhead Transcription Factors/antagonists & inhibitors | - |
dc.subject.MESH | Granulosa Cells/drug effects* | - |
dc.subject.MESH | Granulosa Cells/metabolism | - |
dc.subject.MESH | Hypoxia-Inducible Factor 1/metabolism* | - |
dc.subject.MESH | Insulin-Like Growth Factor I/pharmacology | - |
dc.subject.MESH | Nerve Tissue Proteins/antagonists & inhibitors | - |
dc.subject.MESH | Ovary/drug effects* | - |
dc.subject.MESH | Ovary/metabolism | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/physiology* | - |
dc.subject.MESH | Phosphorylation/drug effects | - |
dc.subject.MESH | Protein Kinases/physiology | - |
dc.subject.MESH | Proto-Oncogene Proteins c-mdm2/metabolism | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Sprague-Dawley | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Signal Transduction/physiology | - |
dc.subject.MESH | TOR Serine-Threonine Kinases | - |
dc.subject.MESH | Vascular Endothelial Growth Factor A/genetics | - |
dc.subject.MESH | Vascular Endothelial Growth Factor A/metabolism* | - |
dc.title | Role of the phosphatidylinositol-3-kinase and extracellular regulated kinase pathways in the induction of hypoxia-inducible factor (HIF)-1 activity and the HIF-1 target vascular endothelial growth factor in ovarian granulosa cells in response to follicle-stimulating hormone | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Hena Alam | - |
dc.contributor.googleauthor | Jennifer Weck | - |
dc.contributor.googleauthor | Evelyn Maizels | - |
dc.contributor.googleauthor | Youngkyu Park | - |
dc.contributor.googleauthor | Eun Jig Lee | - |
dc.contributor.googleauthor | Margaret Ashcroft | - |
dc.contributor.googleauthor | Mary Hunzicker-Dunn | - |
dc.identifier.doi | 10.1210/en.2008-0850 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03050 | - |
dc.relation.journalcode | J00772 | - |
dc.identifier.eissn | 1945-7170 | - |
dc.identifier.pmid | 18845636 | - |
dc.contributor.alternativeName | Lee, Eun Jig | - |
dc.contributor.affiliatedAuthor | Lee, Eun Jig | - |
dc.citation.volume | 150 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 915 | - |
dc.citation.endPage | 928 | - |
dc.identifier.bibliographicCitation | ENDOCRINOLOGY, Vol.150(2) : 915-928, 2009 | - |
dc.identifier.rimsid | 36683 | - |
dc.type.rims | ART | - |
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