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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Critical intermediate steps in Clostridium sordellii lethal toxin-induced apoptosis

Daniel E Voth1, Jimmy D Ballard

  • 1Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, 975 N.E. 10th St., BRC-362A, Oklahoma City, OK 73104, USA.

Biochemical and Biophysical Research Communications
|October 4, 2007
PubMed

Insights

Clostridium sordellii lethal toxin (TcsL) triggers apoptosis by inactivating small GTPases. This study reveals TcsL disrupts the Akt pathway, leading to mitochondrial damage and cell death.

Area of Science:

  • Microbiology
  • Cell Biology
  • Toxicology

Background:

  • Clostridium sordellii lethal toxin (TcsL) is a bacterial toxin that inactivates small GTPases through glucosylation.
  • TcsL induces apoptosis in mammalian cells, but the precise signaling pathways linking toxin action to mitochondrial apoptosis remain unclear.

Purpose of the Study:

  • To investigate the signaling events connecting TcsL-mediated GTPase inactivation to mitochondrial apoptosis.
  • To elucidate the role of the Akt signaling pathway in TcsL-induced cell death.

Main Methods:

  • Analysis of Akt signaling pathway modulation following TcsL intoxication.
  • Assessment of caspase-dependent processing of apoptosis-related proteins like Bcl-x(L) and Bid.
  • Monitoring of downstream targets such as glycogen synthase kinase-3beta.

Main Results:

  • TcsL intoxication rapidly decreased phosphorylated Akt levels, dependent on toxin enzymatic activity.
  • This Akt pathway disruption was followed by caspase-dependent cleavage of Bcl-x(L) and Bid.
  • Declining levels of glycogen synthase kinase-3beta were observed later in intoxication, indicating further apoptotic progression.

Conclusions:

  • TcsL disrupts the Akt signaling pathway, linking GTPase inactivation to mitochondrial apoptosis.
  • The study identifies a cascade of signaling events, including Akt inhibition and caspase activation, culminating in TcsL-induced cell death.

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