Pseudomonas aeruginosa-derived pigment pyocyanin (PCN) has been
proved to induce cell apoptosis mediated by the generation of reactive oxygen
species (ROS), which has been studied mainly in epithelial cells and
neutrophils. However, we previously found that the PCN-producing strain PA14
induces cell apoptosis in human NK cell line NK92 more effectively than in
PCN-deficient strain PA14-phZ1/2 via a yet undetermined mechanism. In the
current study, we found that PCN-induced NK92 cell apoptosis occurs through
mitochondrial damage despite inhibiting intracellular ROS generation.
Intracellular Ca2+ ([Ca2+]i) and Bcl-2 family
proteins act as important “priming signals” for apoptosis. PCN treatment
increased [Ca2+]i in NK92 cells more than twofold after 2
h stimulation, whereas the Ca2+-chelating agent ethylene glycol
tetra-acetic acid (EGTA) inhibited apoptosis. PCN triggered the activation of
Bim, Bid, Bik, Bak, and phospho-Bad in NK92 cells in a concentration-dependent
manner, but these pro-apoptotic Bcl-2 family proteins were not inhibited by
EGTA. In this study, we describe the function of PCN in NK92 cells and identify
mitochondrial damage as the mechanism underlying the apoptosis.
[Ca2+]i and pro-apoptotic Bcl-2 family proteins are
novel targets for PCN-induced apoptosis. Clarification of the cytotoxic
diversity of PCN provides a new therapeutic target for defense from P.
aeruginosa-induced immune cell damage.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.