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

Yun Jong Park, Hyung Joon Ahn, YuSeun Kim, Yuri Cho, Dong Jin Joo, Man Ki Ju

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mycophenolic acid (MPA), widely used to prevent organ transplant rejection, may induce toxicity and impair function in β-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-α gene expression, which points to apoptosis by JNK activation through a MAPKs-dependent pathway. A strong association between RhoGDI-α and Rac1 activation during MPA-induced apoptosis is also consistent with apoptosis through JNK. Suppression of RhoGDI-α 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-α and JNK signaling. We conclude that MPA-induced cell death in primary β-cells and an insulin-secreting cell line proceeds through RhoGDI-α down-regulation linked to Rac1 activation, with subsequent activation of JNK. The RhoGDI-α/Rac1/JNK pathway may present a key to intervention in MPA-induced islet apoptosis.

Original languageEnglish
Pages (from-to)1773-1782
Number of pages10
JournalCellular Signalling
Volume22
Issue number11
DOIs
Publication statusPublished - 2010 Nov 1

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Mycophenolic Acid
Microarray Analysis
Islets of Langerhans
Cell Death
Insulin
Cell Line
Apoptosis
Gene Expression
rac1 GTP-Binding Protein
MAP Kinase Signaling System
Insulin-Secreting Cells
Graft Rejection
Oligonucleotide Array Sequence Analysis
Small Interfering RNA
Down-Regulation
Transplants
Mortality

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

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title = "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",
abstract = "Mycophenolic acid (MPA), widely used to prevent organ transplant rejection, may induce toxicity and impair function in β-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-α gene expression, which points to apoptosis by JNK activation through a MAPKs-dependent pathway. A strong association between RhoGDI-α and Rac1 activation during MPA-induced apoptosis is also consistent with apoptosis through JNK. Suppression of RhoGDI-α 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-α and JNK signaling. We conclude that MPA-induced cell death in primary β-cells and an insulin-secreting cell line proceeds through RhoGDI-α down-regulation linked to Rac1 activation, with subsequent activation of JNK. The RhoGDI-α/Rac1/JNK pathway may present a key to intervention in MPA-induced islet apoptosis.",
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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. / Park, Yun Jong; Ahn, Hyung Joon; Kim, YuSeun; Cho, Yuri; Joo, Dong Jin; Ju, Man Ki.

In: Cellular Signalling, Vol. 22, No. 11, 01.11.2010, p. 1773-1782.

Research output: Contribution to journalArticle

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