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

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 th...

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Autores principales: Huh, K H, Cho, Y, Kim, B S, Do, J H, Park, Y-J, Joo, D J, Kim, M S, Kim, Y S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730420/
https://www.ncbi.nlm.nih.gov/pubmed/23846223
http://dx.doi.org/10.1038/cddis.2013.247
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author Huh, K H
Cho, Y
Kim, B S
Do, J H
Park, Y-J
Joo, D J
Kim, M S
Kim, Y S
author_facet Huh, K H
Cho, Y
Kim, B S
Do, J H
Park, Y-J
Joo, D J
Kim, M S
Kim, Y S
author_sort Huh, K H
collection PubMed
description 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.
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spelling pubmed-37304202013-08-01 The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells Huh, K H Cho, Y Kim, B S Do, J H Park, Y-J Joo, D J Kim, M S Kim, Y S Cell Death Dis Original Article 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. Nature Publishing Group 2013-07 2013-07-11 /pmc/articles/PMC3730420/ /pubmed/23846223 http://dx.doi.org/10.1038/cddis.2013.247 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
Huh, K H
Cho, Y
Kim, B S
Do, J H
Park, Y-J
Joo, D J
Kim, M S
Kim, Y S
The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title_full The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title_fullStr The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title_full_unstemmed The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title_short The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
title_sort role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730420/
https://www.ncbi.nlm.nih.gov/pubmed/23846223
http://dx.doi.org/10.1038/cddis.2013.247
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