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The RhoGDI-alpha/JNK signaling pathway plays a significant role in mycophenolic acid-induced apoptosis in an insulin-secreting cell line

DC Field Value Language
dc.contributor.author김준예-
dc.contributor.author장혜경-
dc.contributor.author허규하-
dc.contributor.author김명수-
dc.contributor.author김유선-
dc.date.accessioned2015-04-24T16:21:01Z-
dc.date.available2015-04-24T16:21:01Z-
dc.date.issued2009-
dc.identifier.issn0898-6568-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/103365-
dc.description.abstractMycophenolic acid (MPA)-induced beta-cell toxicity is an important factor for islet graft function. The signal transduction mechanisms underlying this process have not been fully explored. Using a proteomics approach, we examined protein expression patterns in MPA-treated RIN-5 cells and found that RhoGDI-alpha expression is altered by MPA-treatment. We examined the relationship between RhoGDI-alpha expression and activated JNK during MPA-induced apoptosis. Cells were treated with N-acetyl-cysteine (NAC), caspase inhibitor, JNK inhibitor, guanosine or GTP for 1 h before being treated with MPA. To investigate the regulatory effects of RhoGDI-alpha on JNK activity, we examined cells showing either elevated or reduced expression of RhoGDI-alpha as a result of transfection with cDNA or siRNA constructs, respectively. MPA significantly increased cell death, caspase-3 expression and JNK activation, but it decreased the expression of a protein spot 25 observed by two-dimensional electrophoresis. This protein 25 was identified as RhoGDI-alpha by mass spectrometry. MPA-induced cell death and down-regulation of RhoGDI-alpha were prevented by guanosine, GTP or a JNK inhibitor. However, MPA-induced cell death was partially restored by treatment with a caspase inhibitor, but not by NAC treatment. RhoGDI-alpha expression was not affected by treatment with NAC or caspase inhibitor. Over-expression of RhoGDI-alpha increased cell viability and decreased activated JNK expression following exposure to MPA, whereas knockdown of RhoGDI-alpha enhanced MPA-induced cell death and increased the activation of JNK. In conclusion, MPA induces significant apoptosis in insulin-secreting cells via down-regulation of RhoGDI-alpha linked with increased JNK expression. This RhoGDI-alpha/JNK pathway might be the focus of therapeutic target for the prevention of MPA-induced islet apoptosis.-
dc.description.statementOfResponsibilityopen-
dc.format.extent356~364-
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.MESHAnalysis of Variance-
dc.subject.MESHAnimals-
dc.subject.MESHApoptosis*/drug effects-
dc.subject.MESHBase Sequence-
dc.subject.MESHCaspase 3/metabolism-
dc.subject.MESHCell Line-
dc.subject.MESHElectrophoresis, Gel, Two-Dimensional-
dc.subject.MESHGuanine Nucleotide Dissociation Inhibitors/metabolism*-
dc.subject.MESHInsulin-Secreting Cells/drug effects-
dc.subject.MESHInsulin-Secreting Cells/enzymology-
dc.subject.MESHInsulin-Secreting Cells/metabolism*-
dc.subject.MESHJNK Mitogen-Activated Protein Kinases/metabolism*-
dc.subject.MESHMycophenolic Acid/pharmacology*-
dc.subject.MESHProteomics-
dc.subject.MESHRats-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization-
dc.subject.MESHrho-Specific Guanine Nucleotide Dissociation Inhibitors-
dc.titleThe RhoGDI-alpha/JNK signaling pathway plays a significant role in mycophenolic acid-induced apoptosis in an insulin-secreting cell line-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Surgery (외과학)-
dc.contributor.googleauthorYun-Jong Park-
dc.contributor.googleauthorHyung Joon Ahn-
dc.contributor.googleauthorHye Kyung Chang-
dc.contributor.googleauthorJoon Ye Kim-
dc.contributor.googleauthorKyu Ha Huh-
dc.contributor.googleauthorMyoung Soo Kim-
dc.contributor.googleauthorYu Seun Kim-
dc.identifier.doi10.1016/j.cellsig.2008.11.009-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00956-
dc.contributor.localIdA03494-
dc.contributor.localIdA04344-
dc.contributor.localIdA00785-
dc.contributor.localIdA00424-
dc.relation.journalcodeJ00502-
dc.identifier.eissn1873-3913-
dc.identifier.pmid19041939-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0898656808003392-
dc.subject.keywordMycophenolic acid-
dc.subject.keywordInsulin-secreting cells-
dc.subject.keywordApoptosis-
dc.subject.keywordRhoGDI-α-
dc.subject.keywordJNK-
dc.contributor.alternativeNameKim, Joon Ye-
dc.contributor.alternativeNameChang, Hye Kyung-
dc.contributor.alternativeNameHuh, Kyu Ha-
dc.contributor.alternativeNameKim, Myoung Soo-
dc.contributor.alternativeNameKim, Yu Seun-
dc.contributor.affiliatedAuthorKim, Joon Ye-
dc.contributor.affiliatedAuthorChang, Hye Kyung-
dc.contributor.affiliatedAuthorHuh, Kyu Ha-
dc.contributor.affiliatedAuthorKim, Yu Seun-
dc.contributor.affiliatedAuthorKim, Myoung Soo-
dc.citation.volume21-
dc.citation.number2-
dc.citation.startPage356-
dc.citation.endPage364-
dc.identifier.bibliographicCitationCELLULAR SIGNALLING, Vol.21(2) : 356-364, 2009-
dc.identifier.rimsid37296-
dc.type.rimsART-
Appears in Collections:
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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