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Molecular mechanisms of cell death of mycophenolic acid-treated primary isolated rat islets: implication of mitogen-activated protein kinase activation

Authors
 J.Y. Kim  ;  K.H. Huh  ;  Y.-J. Park  ;  Y. Fang  ;  C.M. Kang  ;  Y.S. Kim 
Citation
 TRANSPLANTATION PROCEEDINGS, Vol.40(8) : 2575-2577, 2008 
Journal Title
 TRANSPLANTATION PROCEEDINGS 
ISSN
 0041-1345 
Issue Date
2008
MeSH
Animals ; Caspase 3/metabolism ; Cell Death/drug effects* ; Enzyme Activation ; Islets of Langerhans/cytology* ; Islets of Langerhans/drug effects* ; Islets of Langerhans/enzymology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Kinetics ; Mitogen-Activated Protein Kinases/metabolism* ; Mycophenolic Acid/pharmacology* ; Rats ; Rats, Inbred Lew ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
Animals ; Caspase 3/metabolism ; Cell Death/drug effects* ; Enzyme Activation ; Islets of Langerhans/cytology* ; Islets of Langerhans/drug effects* ; Islets of Langerhans/enzymology ; JNK Mitogen-Activated Protein Kinases/metabolism ; Kinetics ; Mitogen-Activated Protein Kinases/metabolism* ; Mycophenolic Acid/pharmacology* ; Rats ; Rats, Inbred Lew ; p38 Mitogen-Activated Protein Kinases/metabolism
Abstract
Optimal immunosuppression after pancreas islet transplantation has not yet been established to achieve long-term graft survival. Mycophenolic acid (MPA) is widely used as an immunosuppressive drug after transplantation including among recipients of pancreas islet cells. Previously, we reported MPA-induced islet apoptosis in the HIT-T15 cell line. In this study, we confirmed the effects of MPA on cell death and its potential implications on the mitogen-activated protein kinase (MAPK) family expression levels in primary isolated rat islets. Lewis islets isolated by collagenase digestion were purified by the density gradient method. Cell death was analyzed by methylthiazoletetrazolium assay. Activation of MAPK kinase 4 (MKK4), c-jun N-terminal protein kinase (JNK), p38 MAPK, and caspase-3 cleavage was examined by Western blot analyses. MPA treatments (> 25 micromol/L) increased cell death significantly at 24 hours and in a dose-dependent manner activated MKK4, JNK, and p38 MAPK at 20 hours. Caspase-3 cleavage was also increased by MPA treatment. These results suggested that MPA induced significant cell death among primary isolated rat islets by activation of MKK4, JNK, and p38 MAPK, as well as caspase-3 cleavage.
Full Text
http://www.sciencedirect.com/science/article/pii/S0041134508009779
DOI
10.1016/j.transproceed.2008.07.123
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107591
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