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Illumina-microarray analysis of mycophenolic acid-induced cell death in an insulin-producing cell line and primary rat islet cells: new insights into apoptotic pathways involved

DC Field Value Language
dc.contributor.author김유선-
dc.contributor.author박윤종-
dc.contributor.author조유리-
dc.contributor.author주동진-
dc.contributor.author주만기-
dc.date.accessioned2015-04-23T17:10:56Z-
dc.date.available2015-04-23T17:10:56Z-
dc.date.issued2010-
dc.identifier.issn0898-6568-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/101977-
dc.description.abstractMycophenolic acid (MPA), widely used to prevent organ transplant rejection, may induce toxicity and impair function in beta-cells. Mechanisms of MPA-induced cell death have not been fully explored. In this study, we examined gene expression patterns in INS-1E cells and isolated primary rat islets following MPA treatment using the Illumina-cDNA microarray. The MPA treatment decreases RhoGDI-alpha gene expression, which points to apoptosis by JNK activation through a MAPKs-dependent pathway. A strong association between RhoGDI-alpha and Rac1 activation during MPA-induced apoptosis is also consistent with apoptosis through JNK. Suppression of RhoGDI-alpha using siRNA and gene over-expression both affected the cell death rate, consistent with Rac1 activation and downstream activation of MAPKs signaling. We confirmed that Rac1 protein mediates the interaction between RhoGDI-alpha and JNK signaling. We conclude that MPA-induced cell death in primary beta-cells and an insulin-secreting cell line proceeds through RhoGDI-alpha down-regulation linked to Rac1 activation, with subsequent activation of JNK. The RhoGDI-alpha/Rac1/JNK pathway may present a key to intervention in MPA-induced islet apoptosis.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1773~1782-
dc.relation.isPartOfCELLULAR SIGNALLING-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis*-
dc.subject.MESHGene Expression Regulation-
dc.subject.MESHGuanine Nucleotide Dissociation Inhibitors/genetics-
dc.subject.MESHGuanine Nucleotide Dissociation Inhibitors/metabolism-
dc.subject.MESHInsulin/metabolism-
dc.subject.MESHInsulin-Secreting Cells/drug effects-
dc.subject.MESHInsulin-Secreting Cells/metabolism*-
dc.subject.MESHIslets of Langerhans/drug effects-
dc.subject.MESHIslets of Langerhans/metabolism*-
dc.subject.MESHJNK Mitogen-Activated Protein Kinases/metabolism-
dc.subject.MESHMAP Kinase Signaling System-
dc.subject.MESHMycophenolic Acid/toxicity*-
dc.subject.MESHOligonucleotide Array Sequence Analysis-
dc.subject.MESHRNA Interference-
dc.subject.MESHRNA, Small Interfering/metabolism-
dc.subject.MESHRats-
dc.subject.MESHrac1 GTP-Binding Protein/metabolism-
dc.subject.MESHrho-Specific Guanine Nucleotide Dissociation Inhibitors-
dc.titleIllumina-microarray analysis of mycophenolic acid-induced cell death in an insulin-producing cell line and primary rat islet cells: new insights into apoptotic pathways involved-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorYun-Jong Park-
dc.contributor.googleauthorHyung Joon Ahn-
dc.contributor.googleauthorYu Seun Kim-
dc.contributor.googleauthorYuri Cho-
dc.contributor.googleauthorDong Jin Joo-
dc.contributor.googleauthorMan Ki Ju-
dc.identifier.doi10.1016/j.cellsig.2010.07.005-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00785-
dc.contributor.localIdA01603-
dc.contributor.localIdA03872-
dc.contributor.localIdA03948-
dc.contributor.localIdA03949-
dc.relation.journalcodeJ00502-
dc.identifier.eissn1873-3913-
dc.identifier.pmid20637860-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0898656810001981-
dc.subject.keywordMycophenolic acid-
dc.subject.keywordINS-1E-
dc.subject.keywordIslet cells-
dc.subject.keywordApoptosis-
dc.subject.keywordRhoGDI-α-
dc.subject.keywordRac1-
dc.contributor.alternativeNameKim, Yu Seun-
dc.contributor.alternativeNamePark, Yun Jong-
dc.contributor.alternativeNameCho, Yu Ri-
dc.contributor.alternativeNameJoo, Dong Jin-
dc.contributor.alternativeNameJoo, Man Ki-
dc.contributor.affiliatedAuthorKim, Yu Seun-
dc.contributor.affiliatedAuthorPark, Yun Jong-
dc.contributor.affiliatedAuthorCho, Yu Ri-
dc.contributor.affiliatedAuthorJoo, Dong Jin-
dc.contributor.affiliatedAuthorJoo, Man Ki-
dc.citation.volume22-
dc.citation.number11-
dc.citation.startPage1773-
dc.citation.endPage1782-
dc.identifier.bibliographicCitationCELLULAR SIGNALLING, Vol.22(11) : 1773-1782, 2010-
dc.identifier.rimsid50987-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers

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