학술논문
Peroxiredoxin I deficiency increases pancreatic [beta]-cell apoptosis after streptozotocin stimulation via the AKT/GSK3[beta] signaling pathway
Document Type
Academic Journal
Author
Source
Molecular Medicine Reports. September 2020, Vol. 22 Issue 3, p1831, 8 p.
Subject
Language
English
ISSN
1791-2997
Abstract
Introduction Diabetes is a disease that often manifests as hyperglycemia and is caused both by genetic and environmental factors. Diabetes is classified into type I and type II diabetes. Type [...]
Apoptosis of pancreatic [beta]-cells is involved in the pathogenesis of type I and II diabetes. Peroxiredoxin I (Prx I) serves an important role in regulating cellular apoptosis; however, the role of Prx I in pancreatic [beta]-cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)-induced apoptosis of pancreatic [beta]-cells was investigated. The expression level of Prx I was decreased by STZ treatment in a time-dependent manner, and apoptosis of Prx I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx I knockout mice, compared with wild-type and Prx II knockout mice. AKT and glycogen synthase kinase (GSK)-3[beta] phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated [beta]-catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx I mediated STZ-induced pancreatic [beta]-cell death in vivo and in vitro by regulating the AKT/GSK-3[beta]/[beta]-catenin signaling pathway, as well as NF-[kappa]B signaling. These findings provide a theoretical basis for treatment of pancreatic damage. Key words: peroxiredoxin I, apoptosis, streptozotocin, [beta]-cell, glycogen synthase kinase-3[beta] signaling
Apoptosis of pancreatic [beta]-cells is involved in the pathogenesis of type I and II diabetes. Peroxiredoxin I (Prx I) serves an important role in regulating cellular apoptosis; however, the role of Prx I in pancreatic [beta]-cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)-induced apoptosis of pancreatic [beta]-cells was investigated. The expression level of Prx I was decreased by STZ treatment in a time-dependent manner, and apoptosis of Prx I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx I knockout mice, compared with wild-type and Prx II knockout mice. AKT and glycogen synthase kinase (GSK)-3[beta] phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated [beta]-catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx I mediated STZ-induced pancreatic [beta]-cell death in vivo and in vitro by regulating the AKT/GSK-3[beta]/[beta]-catenin signaling pathway, as well as NF-[kappa]B signaling. These findings provide a theoretical basis for treatment of pancreatic damage. Key words: peroxiredoxin I, apoptosis, streptozotocin, [beta]-cell, glycogen synthase kinase-3[beta] signaling