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 language | English |
|---|---|
| Pages (from-to) | 1773-1782 |
| Number of pages | 10 |
| Journal | Cellular Signalling |
| Volume | 22 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2010 Nov 1 |
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All Science Journal Classification (ASJC) codes
- Cell Biology
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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 journal › Article
TY - JOUR
T1 - Illumina-microarray analysis of mycophenolic acid-induced cell death in an insulin-producing cell line and primary rat islet cells
T2 - New insights into apoptotic pathways involved
AU - Park, Yun Jong
AU - Ahn, Hyung Joon
AU - Kim, YuSeun
AU - Cho, Yuri
AU - Joo, Dong Jin
AU - Ju, Man Ki
PY - 2010/11/1
Y1 - 2010/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77955661974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955661974&partnerID=8YFLogxK
U2 - 10.1016/j.cellsig.2010.07.005
DO - 10.1016/j.cellsig.2010.07.005
M3 - Article
VL - 22
SP - 1773
EP - 1782
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
IS - 11
ER -