title: Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis.
abstract: Pancreatic β-cell dysfunction is a critical component in the pathogenesis of diabetes. Endoplasmic reticulum (ER) stress is one of the factors that induces pancreatic β-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 β-cell apoptosis. Induction of DRP-1 expression significantly promoted ER stress-induced apoptosis in the DRP-1 WT (DRP-1 wild- type) inducible β-cell line, but not in the DRP-1 K38A (a dominant negative mutant of DRP-1) inducible β-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 β-cells under ER stress conditions. These results indicate that DRP-1 mediates ER stress-induced pancreatic β-cell apoptosis.
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Xiuli
authors.initials: X
authors.lastname: Men
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.forename: Wenying
authors.initials: W
authors.lastname: Yang
authors.forename: Jinning
authors.initials: J
authors.lastname: Lou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D014415:Tunicamycin; D019284:Thapsigargin; D045304:Cytochromes c; D053148:Caspase 3; C519851:Dnm1l protein, rat; D034281:Dynamins