title: The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells.
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.
authors.affiliation: Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Do
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Park
authors.forename: D J
authors.initials: DJ
authors.lastname: Joo
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009173:Mycophenolic Acid / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D061251:Primary Cell Culture; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D059467:Transcriptome / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; C495697:Txn1 protein, rat; D013879:Thioredoxins; D020928:Mitogen-Activated Protein Kinases; D009173:Mycophenolic Acid