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

Abstract

HighlightsShiga toxin (Stx) rapidly reduces the level of short-lived anti-apoptotic proteins.Stx induces activation of caspase 9 and apoptosis.Proteasome inhibitors prevent the reduction of anti-apoptotic proteins.Proteasome inhibitors suppress Stx-induced apoptosis.Bortezomib prolongs the survival of mice challenged with a lethal dose of Stx.

M‐COPA, a novel Golgi system disruptor, suppresses apoptosis induced by Shiga toxin

“…, ; Hattori et al . ). Treatment with M‐COPA also suppressed the reduction of FLIP and Mcl‐1 proteins indicating that M‐COPA interferes with an event upstream of the degradation of anti‐apoptotic proteins.…”

“…, ; Hattori et al . ), which is reflected in proteolytic cleavage of poly(ADP‐ribose) polymerase (PARP) (Nicholson et al . ; Tewari et al .…”

“…; Hattori et al . ). We and others reported that apoptosis induced by Stx is mediated by the proteasomal degradation of anti‐apoptotic proteins and subsequent activation of caspases (Erwert et al .…”

“…, ; Hattori et al . ). We also showed that pharmacological inhibition of the proteasome prevents the reduction of anti‐apoptotic proteins and apoptosis in Stx‐treated cells (Hattori et al .…”

“…We also showed that pharmacological inhibition of the proteasome prevents the reduction of anti‐apoptotic proteins and apoptosis in Stx‐treated cells (Hattori et al . ). This suggests that inhibition of Stx‐induced apoptosis is a promising approach for Stx detoxification.…”