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NO donor induces Nec‐1‐inhibitable, but RIP1‐independent, necrotic cell death in pancreatic β‐cells
Author(s) -
Tamura Yoshiaki,
Chiba Yuko,
Tanioka Toshihiro,
Shimizu Nobuyuki,
Shinozaki Shohei,
Yamada Marina,
Kaneki Kentaro,
Mori Seijiro,
Araki Atsushi,
Ito Hideki,
Kaneki Masao
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2011.08.028
Subject(s) - programmed cell death , necrosis , necroptosis , apoptosis , microbiology and biotechnology , cell , tumor necrosis factor alpha , biology , cancer research , chemistry , immunology , biochemistry , genetics
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.