title: NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell death in pancreatic β-cells.
abstract: Nitric oxide (NO) has been implicated in pancreatic β-cell death in the development of diabetes. The mechanisms underlying NO-induced β-cell death have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis. Here, we show that NO donor-induced β-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1 knockdown neither inhibited cell death nor altered the protective effects of necrostatin-1 in NO donor-treated β-cells. These results indicate that NO donor induces necrostatin-1-inhibitable necrotic β-cell death independent of RIP1. Our findings raise the possibility that NO-mediated β-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes.
authors: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Charlestown, MA 02129, USA.
authors: Yoshiaki
authors: Y
authors: Tamura
authors: Yuko
authors: Y
authors: Chiba
authors: Toshihiro
authors: T
authors: Tanioka
authors: Nobuyuki
authors: N
authors: Shimizu
authors: Shohei
authors: S
authors: Shinozaki
authors: Marina
authors: M
authors: Yamada
authors: Kentaro
authors: K
authors: Kaneki
authors: Seijiro
authors: S
authors: Mori
authors: Atsushi
authors: A
authors: Araki
authors: Hideki
authors: H
authors: Ito
authors: Masao
authors: M
authors: Kaneki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology*; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism; D055785:Gene Knockdown Techniques; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D024243:HMGB1 Protein; D007093:Imidazoles; D007211:Indoles; D020030:Nitric Oxide Donors; D034741:RNA, Small Interfering; C507699:necrostatin-1; D026422:S-Nitrosoglutathione; D000255:Adenosine Triphosphate; D051057:Proto-Oncogene Proteins c-akt; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D021984:Cyclophilin A