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The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells

Authors
 KH Huh  ;  Y Cho  ;  BS Kim  ;  JH Do  ;  Y-J Park  ;  DJ Joo  ;  MS Kim  ;  YS Kim 
Citation
 CELL DEATH & DISEASE, Vol.4 : 721, 2013 
Journal Title
 CELL DEATH & DISEASE 
Issue Date
2013
MeSH
Immunosuppressive Agents/pharmacology* ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/physiology* ; Islets of Langerhans Transplantation ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Mycophenolic Acid/pharmacology* ; Oligonucleotide Array Sequence Analysis ; Primary Cell Culture ; Rats, Inbred Lew ; Reactive Oxygen Species/metabolism ; Thioredoxins/genetics* ; Thioredoxins/metabolism ; Thioredoxins/physiology ; Transcriptome/drug effects
Keywords
Immunosuppressive Agents/pharmacology* ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/physiology* ; Islets of Langerhans Transplantation ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases/genetics ; Mitogen-Activated Protein Kinases/metabolism ; Mycophenolic Acid/pharmacology* ; Oligonucleotide Array Sequence Analysis ; Primary Cell Culture ; Rats, Inbred Lew ; Reactive Oxygen Species/metabolism ; Thioredoxins/genetics* ; Thioredoxins/metabolism ; Thioredoxins/physiology ; Transcriptome/drug effects
Abstract
Mycophenolic acid (MPA) is one of many effective immunosuppressive drugs. However, MPA can induce cellular toxicity and impair cellular function in β-cells. To explore the effects of MPA and the relation between MPA and Trx-1, we used various methods, including an Illumina microarray, to identify the genes regulated during pancreatic β-cell death following MPA treatment. INS-1E cells (a pancreatic β-cell line) and isolated rat islets were treated with MPA for 12, 24, or 36 h, and subsequent microarray analysis showed that (Trx1) gene expression was significantly reduced by MPA. Further, Trx1 overexpression increased the cell viability, decreased the activations of c-jun N-terminal kinase (JNK) and caspase-3 by MPA, and attenuated ROS upregulation by MPA. Furthermore, siRNA knockdown of Trx1 increased MPA-induced cell death and the activations of p-JNK and caspase-3, and MPA significantly provoked the apoptosis of insulin-secreting cells via Trx1 downregulation. Our findings suggest that the prevention of Trx1 downregulation in response to MPA is critical for successful islet transplantation.
Files in This Item:
T201301985.pdf Download
DOI
10.1038/cddis.2013.247
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Do, Ji Hye(도지혜)
Park, Youn Joon(박윤준)
Cho, Yu Ri(조유리)
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87129
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