Molecular Mechanisms of Cell Death of Mycophenolic Acid-Treated Primary Isolated Rat Islets: Implication of Mitogen-Activated Protein Kinase Activation

J. Y. Kim, K. H. Huh, Y. J. Park, Y. Fang, C. M. Kang, Y. S. Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 μmol/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.

Original languageEnglish
Pages (from-to)2575-2577
Number of pages3
JournalTransplantation Proceedings
Volume40
Issue number8
DOIs
Publication statusPublished - 2008 Oct 1

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Mycophenolic Acid
Mitogen-Activated Protein Kinases
Cell Death
p38 Mitogen-Activated Protein Kinases
Caspase 3
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 4
Pancreas Transplantation
Islets of Langerhans Transplantation
Mitogen-Activated Protein Kinase 3
JNK Mitogen-Activated Protein Kinases
Collagenases
Graft Survival
Immunosuppressive Agents
Islets of Langerhans
Immunosuppression
Pancreas
Digestion
Transplantation
Western Blotting

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

Cite this

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title = "Molecular Mechanisms of Cell Death of Mycophenolic Acid-Treated Primary Isolated Rat Islets: Implication of Mitogen-Activated Protein Kinase Activation",
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 μmol/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.",
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Molecular Mechanisms of Cell Death of Mycophenolic Acid-Treated Primary Isolated Rat Islets : Implication of Mitogen-Activated Protein Kinase Activation. / Kim, J. Y.; Huh, K. H.; Park, Y. J.; Fang, Y.; Kang, C. M.; Kim, Y. S.

In: Transplantation Proceedings, Vol. 40, No. 8, 01.10.2008, p. 2575-2577.

Research output: Contribution to journalArticle

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