Open AccessProteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin
Author(s) -
Hattori Takayuki,
Watanabe-Takahashi Miho,
Ohoka Nobumichi,
Hamabata Takashi,
Furukawa Koichi,
Nishikawa Kiyotaka,
Naito Mikihiko
Publication year - 2015
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2015.06.005
Subject(s) - proteasome , apoptosis , bortezomib , shiga toxin , proteasome inhibitor , programmed cell death , toxin , caspase , biology , caspase 3 , cancer research , immunology , microbiology and biotechnology , biochemistry , multiple myeloma , virulence , gene
Shiga toxin (Stx) causes fatal systemic complications. Stx induces apoptosis, but the mechanism of which is unclear. We report that Stx induced rapid reduction of short‐lived anti‐apoptotic proteins followed by activation of caspase 9 and the progression of apoptosis. Proteasome inhibitors prevented the reduction of anti‐apoptotic proteins, and inhibited caspase activation and apoptosis, suggesting that the reduction of anti‐apoptotic proteins is a prerequisite for Stx‐induced apoptosis. A clinically approved proteasome inhibitor, bortezomib, prolonged the survival of mice challenged by Stx. These results imply that proteasome inhibition may be a novel approach to prevent the fatal effects of Stx.