Phosphodiesterase inhibitors control A172 human glioblastoma cell death through cAMP-mediated activation of protein kinase A and Epac1/Rap1 pathways
DC Field | Value | Language |
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dc.contributor.author | Moon, Eun-Yi | - |
dc.contributor.author | Lee, Geun-Hee | - |
dc.contributor.author | Lee, Myung-Shik | - |
dc.contributor.author | Kim, Hwan-Mook | - |
dc.contributor.author | Lee, Jae-Wook | - |
dc.date.available | 2020-02-29T06:45:35Z | - |
dc.date.created | 2020-02-05 | - |
dc.date.issued | 2012-02-27 | - |
dc.identifier.issn | 0024-3205 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/16575 | - |
dc.description.abstract | Aims: We investigated whether cAMP-mediated protein kinase A(PKA) and Epac1/Rap1 pathways differentially affect brain tumor cell death using 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone(rolipram), specific phosphodiesterase type IV(PDE IV) inhibitor. Main methods: A172 and U87MG human glioblastoma cells were used. Percentage of cell survival was determined by MTT assay. PKA and Epac1/Rap1 activation was determined by western blotting and pull-down assay, respectively. Cell cycle and hypodiploid cell formation were assessed by flow cytometry analysis. Key findings: Non-specific PDE inhibitors, isobutylmethylxanthine(IBMX) and theophylline reduce survival percentage of A172 and U87MG cells. The expression of PDE4A and PDE4B was detected in A172 and U87MG cells. Rolipram-treated A172 or U87MG cell survival was lower in the presence of forskolin, adenylate cyclase activator, than that in its absence. Co-treatment with rolipram and forskolin also enhanced CREB phosphorylation on serine 133 that was inhibited by H-89, PKA inhibitor and cAMP-responsive guanine nucleotide exchange factor 1(Epac1), a Rap GDP exchange factor-mediated Rap1 activity in A172 cells. When A172 cells were treated with cell-permeable dibutyryl-cAMP(dbcAMP), PKA activator or 8-(4-chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate(CPT), Epac1 activator, basal level of cell death was increased and cell cycle was arrested at the phase of G2/M. Rolipram-induced A172 cell death was also increased by the co-treatment with dbcAMP or CPT, but it was inhibited by the pre-treatment with H-89. Significance: These findings demonstrate that PKA and Epac1/Rap1 pathways could cooperatively play a role in rolipram-induced brain tumor cell death. It suggests that rolipram might regulate glioblastoma cell density through dual pathways of PKA- and Epac1/Rap1 -mediated cell death and cell cycle arrest. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | - |
dc.relation.isPartOf | LIFE SCIENCES | - |
dc.subject | EPAC1-MEDIATED RAP1 ACTIVATION | - |
dc.subject | CHRONIC LYMPHOCYTIC-LEUKEMIA | - |
dc.subject | CYCLIC-AMP SUPPRESSION | - |
dc.subject | MICROGLIAL CELLS | - |
dc.subject | NITRIC-OXIDE | - |
dc.subject | GROWTH | - |
dc.subject | EPAC | - |
dc.subject | NEUROFIBROMATOSIS-1 | - |
dc.subject | SENSITIVITY | - |
dc.subject | APOPTOSIS | - |
dc.title | Phosphodiesterase inhibitors control A172 human glioblastoma cell death through cAMP-mediated activation of protein kinase A and Epac1/Rap1 pathways | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000301015000009 | - |
dc.identifier.doi | 10.1016/j.lfs.2011.12.010 | - |
dc.identifier.bibliographicCitation | LIFE SCIENCES, v.90, no.9-10, pp.373 - 380 | - |
dc.identifier.scopusid | 2-s2.0-84862808228 | - |
dc.citation.endPage | 380 | - |
dc.citation.startPage | 373 | - |
dc.citation.title | LIFE SCIENCES | - |
dc.citation.volume | 90 | - |
dc.citation.number | 9-10 | - |
dc.contributor.affiliatedAuthor | Kim, Hwan-Mook | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Rolipram | - |
dc.subject.keywordAuthor | PDE | - |
dc.subject.keywordAuthor | Glioblastoma | - |
dc.subject.keywordAuthor | cAMP | - |
dc.subject.keywordAuthor | PKA | - |
dc.subject.keywordAuthor | Epac1 | - |
dc.subject.keywordAuthor | Rap1 | - |
dc.subject.keywordPlus | EPAC1-MEDIATED RAP1 ACTIVATION | - |
dc.subject.keywordPlus | CHRONIC LYMPHOCYTIC-LEUKEMIA | - |
dc.subject.keywordPlus | CYCLIC-AMP SUPPRESSION | - |
dc.subject.keywordPlus | MICROGLIAL CELLS | - |
dc.subject.keywordPlus | NITRIC-OXIDE | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | EPAC | - |
dc.subject.keywordPlus | NEUROFIBROMATOSIS-1 | - |
dc.subject.keywordPlus | SENSITIVITY | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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