Cited 23 times in
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 |
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dc.contributor.author | 김준예 | - |
dc.contributor.author | 장혜경 | - |
dc.contributor.author | 허규하 | - |
dc.contributor.author | 김명수 | - |
dc.contributor.author | 김유선 | - |
dc.date.accessioned | 2015-04-24T16:21:01Z | - |
dc.date.available | 2015-04-24T16:21:01Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0898-6568 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/103365 | - |
dc.description.abstract | Mycophenolic 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.statementOfResponsibility | open | - |
dc.format.extent | 356~364 | - |
dc.relation.isPartOf | CELLULAR SIGNALLING | - |
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 | Analysis of Variance | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis*/drug effects | - |
dc.subject.MESH | Base Sequence | - |
dc.subject.MESH | Caspase 3/metabolism | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Electrophoresis, Gel, Two-Dimensional | - |
dc.subject.MESH | Guanine Nucleotide Dissociation Inhibitors/metabolism* | - |
dc.subject.MESH | Insulin-Secreting Cells/drug effects | - |
dc.subject.MESH | Insulin-Secreting Cells/enzymology | - |
dc.subject.MESH | Insulin-Secreting Cells/metabolism* | - |
dc.subject.MESH | JNK Mitogen-Activated Protein Kinases/metabolism* | - |
dc.subject.MESH | Mycophenolic Acid/pharmacology* | - |
dc.subject.MESH | Proteomics | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | - |
dc.subject.MESH | rho-Specific Guanine Nucleotide Dissociation Inhibitors | - |
dc.title | The RhoGDI-alpha/JNK signaling pathway plays a significant role in mycophenolic acid-induced apoptosis in an insulin-secreting cell line | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학) | - |
dc.contributor.googleauthor | Yun-Jong Park | - |
dc.contributor.googleauthor | Hyung Joon Ahn | - |
dc.contributor.googleauthor | Hye Kyung Chang | - |
dc.contributor.googleauthor | Joon Ye Kim | - |
dc.contributor.googleauthor | Kyu Ha Huh | - |
dc.contributor.googleauthor | Myoung Soo Kim | - |
dc.contributor.googleauthor | Yu Seun Kim | - |
dc.identifier.doi | 10.1016/j.cellsig.2008.11.009 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00956 | - |
dc.contributor.localId | A03494 | - |
dc.contributor.localId | A04344 | - |
dc.contributor.localId | A00785 | - |
dc.contributor.localId | A00424 | - |
dc.relation.journalcode | J00502 | - |
dc.identifier.eissn | 1873-3913 | - |
dc.identifier.pmid | 19041939 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0898656808003392 | - |
dc.subject.keyword | Mycophenolic acid | - |
dc.subject.keyword | Insulin-secreting cells | - |
dc.subject.keyword | Apoptosis | - |
dc.subject.keyword | RhoGDI-α | - |
dc.subject.keyword | JNK | - |
dc.contributor.alternativeName | Kim, Joon Ye | - |
dc.contributor.alternativeName | Chang, Hye Kyung | - |
dc.contributor.alternativeName | Huh, Kyu Ha | - |
dc.contributor.alternativeName | Kim, Myoung Soo | - |
dc.contributor.alternativeName | Kim, Yu Seun | - |
dc.contributor.affiliatedAuthor | Kim, Joon Ye | - |
dc.contributor.affiliatedAuthor | Chang, Hye Kyung | - |
dc.contributor.affiliatedAuthor | Huh, Kyu Ha | - |
dc.contributor.affiliatedAuthor | Kim, Yu Seun | - |
dc.contributor.affiliatedAuthor | Kim, Myoung Soo | - |
dc.citation.volume | 21 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 356 | - |
dc.citation.endPage | 364 | - |
dc.identifier.bibliographicCitation | CELLULAR SIGNALLING, Vol.21(2) : 356-364, 2009 | - |
dc.identifier.rimsid | 37296 | - |
dc.type.rims | ART | - |
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