Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic -cell apoptosis. uri icon

abstract

  • Pancreatic -cell dysfunction is a critical component in the pathogenesis of diabetes. Endoplasmic reticulum (ER) stress is one of the factors that induces pancreatic -cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we report that a mitochondrial fission modulator, dynamin-related protein 1 (DRP-1), plays an important role in ER stress-induced -cell apoptosis. Induction of DRP-1 expression significantly promoted ER stress-induced apoptosis in the DRP-1 WT (DRP-1 wild- type) inducible -cell line, but not in the DRP-1 K38A (a dominant negative mutant of DRP-1) inducible -cell line. We further demonstrated that the mitochondrial membrane potential decreased, and that cytochrome c release, caspase-3 activation and generation of reactive oxygen species (ROS) were enhanced by induction of DRP-1 WT, but prevented by DRP-1 K38A in pancreatic -cells under ER stress conditions. These results indicate that DRP-1 mediates ER stress-induced pancreatic -cell apoptosis.

published proceedings

  • Int J Mol Med

author list (cited authors)

  • Peng, L., Men, X., Zhang, W., Wang, H., Xu, S., Xu, M., ... Lou, J.

citation count

  • 28

complete list of authors

  • Peng, Liang||Men, Xiuli||Zhang, Wenjian||Wang, Haiyan||Xu, Shiqing||Xu, Mei||Xu, Yaping||Yang, Wenying||Lou, Jinning

publication date

  • August 2011