Proteasome inhibitors prevent cell death and prolong survival of mice challenged by Shiga toxin.
FEBS Open Bio
; 5: 605-14, 2015.
Article
em En
| MEDLINE
| ID: mdl-26273560
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.
Apoptosis; Apoptosis inhibitory proteins; BRZ, bortezomib; CHX, cycloheximide; ER, endoplasmic reticulum; FLIP, FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein; Mcl-1, myeloid cell leukemia 1; PARP, Poly(ADP-ribose) polymerase; PI, propidium iodide; Proteasome; Proteasome inhibitor; STEC, Shiga toxin-producing Escherichia coli; Shiga toxin; Stx, Shiga toxin; c-IAP1, cellular inhibitor of apoptosis protein 1
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MEDLINE
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En
Ano de publicação:
2015
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Article