Proteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin.

Abstract:

: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.

journal_name

FEBS Open Bio

journal_title

FEBS open bio

authors

Hattori T,Watanabe-Takahashi M,Ohoka N,Hamabata T,Furukawa K,Nishikawa K,Naito M

doi

10.1016/j.fob.2015.06.005

subject

Has Abstract

pub_date

2015-06-12 00:00:00

pages

605-14

issn

2211-5463

pii

S2211-5463(15)00059-5

journal_volume

5

pub_type

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