Work

Correction: Involvement of Dynamin-Related Protein 1 in Free Fatty Acid-Induced INS-1-Derived Cell Apoptosis

Year: 2013

Type: erratum

Abstract: Elevated extracellular free fatty acids (FFAs) can induce pancreatic beta cell apoptosis, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2D).Mitochondrial dysfunction has been implicated in FFA-induced beta cell apoptosis.However, molecular mechanisms linking mitochondrial dysfunction and FFA-induced beta cell apoptosis are not clear.Dynamin-related protein 1 (DRP-1) is a mitochondrial fission modulator.In this study, we investigated its role in FFAinduced INS-1 beta cell apoptosis.DRP-1 protein was promptly induced in INS-1 cells and rat islets after stimulation by FFAs, and this DRP-1 upregulation was accompanied by increased INS-1 cell apoptosis.Induction of DRP-1 expression significantly promoted FFA-induced apoptosis in DRP-1 WT (DRP-1 wild type) inducible INS-1-derived cell line, but not in DRP-1K38A (a dominant negative mutant of DRP-1) inducible INS-1-derived cell line.To validate these in vitro results, we transplanted DRP-1 WT or DRP-1 K38A cells into renal capsules of streptozotocin (STZ)-treated diabetic mice to study the apoptosis in xenografts.Consistent with the in vitro results, the over-expression of DRP-1 led to aggravated INS-1-derived cell apoptosis triggered by FFAs.In contrast, dominant-negative suppression of DRP-1 function as represented by DRP-1 K38A significantly prevented FFA-induced apoptosis in xenografts.It was further demonstrated that mitochondrial membrane potential decreased, while cytochrome c release, caspase-3 activation, and generation of reactive oxygen species (ROS) were enhanced by the induction of DRP-1WT, but prevented by DRP-1 K38A in INS-1-derived cells under FFA stimulation.These results indicated that DRP-1 mediates FFA-induced INS-1-derived cell apoptosis, suggesting that suppression of DRP-1 is a potentially useful therapeutic strategy for protecting against beta cell loss that leads to type 2 diabetes.

Source: PLoS ONE

DOI: 10.1371/annotation/f8ab435d-accb-4383-8784-23e6edf82f56