Journal
MICROBIAL PATHOGENESIS
Volume 29, Issue 5, Pages 267-278Publisher
ACADEMIC PRESS LTD
DOI: 10.1006/mpat.2000.0390
Keywords
Actinobacillus actinomycetemcomitans; RTX toxins; apoptosis; caspases; mitochondria
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Funding
- NIDCR NIH HHS [DE12305] Funding Source: Medline
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Certain pore-forming bacterial toxins, including the leukotoxin (Ltx) produced by Actinobacillus actinomycetemcomitans, induce apoptosis in susceptible target cells. Although binding to the target cell surface represents the first step in the initiation of this process, the downstream events leading to toxin-induced apoptotic cell death have not been identified. Perturbation of mitochondrial function has been shown to have a major role in regulating progression of apoptosis initiated by exposure to numerous stimuli. Using Ltx as a model, the aim of this study was to evaluate whether induction of apoptosis by pore-forming toxins follows a similar paradigm. After exposure to Ltx, Epstein-Barr virus transformed B cells (JY cell line) exhibited the classical morphological features of apoptosis including decreased cell size, plasma membrane blebbing, selective alterations in plasma membrane permeability and condensation of nuclear DNA. The morphologic changes were accompanied by swelling of the mitochondria, a decrease in mitochondrial transmembrane potential (Psi (m)), hyperproduction of reactive oxygen intermediates (ROIs) and release of cytochrome c from the intermembrane space. Subsequently, we detected activation of the cysteine aspartate-specific proteases (caspases)-3 and -9, cleavage of the nuclear DNA repair enzyme, poly(ADP-ribose)polymerase (PARP) and internucleosomal DNA fragmentation. These results indicate that perturbation of mitochondrial structure and function, in concert with activation of specific caspases, initiate the effector phase of Ltx-induced apoptosis. (C) 2000 Academic Press.
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