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Mycophenolic Acid Induces Islet Apoptosis by Regulating Mitogen-Activated Protein Kinase Activation

Authors
 J.Y. Kim  ;  S.Y. Yoon  ;  J. Park  ;  Y.S. Kim 
Citation
 TRANSPLANTATION PROCEEDINGS, Vol.38(10) : 3277-3279, 2006 
Journal Title
 TRANSPLANTATION PROCEEDINGS 
ISSN
 0041-1345 
Issue Date
2006
MeSH
Apoptosis/drug effects* ; Caspase 3/metabolism ; Cell Line ; Humans ; Insulin/metabolism ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/cytology* ; Islets of Langerhans/drug effects ; Islets of Langerhans/physiology* ; Mitogen-Activated Protein Kinases/drug effects ; Mitogen-Activated Protein Kinases/metabolism* ; Mycophenolic Acid/pharmacology*
Abstract
Mycophenolic acid (MPA), an inosine monophosphate dehydrogenase inhibitor, is widely used as an immunosuppressive drug after transplantations including those of pancreas islet cells. However, recent reports have indicated that MPA has apoptotic effects on islet cells in vitro. To study the effect of MPA on islet cells and determine its mechanism, we used an insulin secreting cell-line, HIT-T15. We examined mitogen-activated protein kinase (MAPK) activation after MPA treatment, and determining cell death levels using methylthiazdetetrazolium assays. The activations of extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK and caspase-3 cleavage were measured by Western blotting. MPA (1, 10, 30 micromol/L) increased cell death and caspase-3 cleavage within 24 hours. Exogenous 500 micromol/L guanosine reversed the MPA-induced islet cell death, but exogenous adenosine did not. MPA 10 micromol/L induced cell apoptosis and increased the activations of JNK, ERK, and p38 MAPK. Furthermore, exogenous guanosine, but not exogenous adenosine, reversed these effects induced by MPA. This study demonstrated that MPA may induce islet apoptosis in HIT-T15 cells by increasing activations of JNK, ERK, and p38 MAPK in a guanosine-dependent manner.
Full Text
http://www.sciencedirect.com/science/article/pii/S0041134506013534
DOI
10.1016/j.transproceed.2006.10.124
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/110556
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