The bacterial redox protein azurin induces apoptosis in J774 macrophages through complex formation and stabilization of the tumor suppressor protein p53.
Two redox proteins, azurin and cytochrome c(551) elaborated by Pseudomonas aeruginosa, demonstrate significant cytotoxic activity towards macrophages. Azurin can enter macrophages, localize in the cytosol and nuclear fractions, and induce apoptosis. Two redox-negative mutants of azurin have less cytotoxicity than does wild-type (wt) azurin. Azurin has been shown to form a complex with the tumor suppressor protein p53, a known inducer of apoptosis, thereby stabilizing it and enhancing its intracellular level. A higher level of reactive oxygen species (ROS), generated during treatment of macrophages with wt azurin, correlates with its cytotoxicity. Treatment with some ROS-removing antioxidants greatly reduces azurin-mediated cytotoxicity, thus demonstrating a novel virulence property of this bacterial redox protein.
Yamada
Tohru
T
Department of Microbiology & Immunology, University of Illinois College of Medicine, Chicago 60612, USA.
Goto
Masatoshi
M
Punj
Vasu
V
Zaborina
Olga
O
Kimbara
Kazuhide
K
Das Gupta
T K
TK
Chakrabarty
A M
AM
D000818:Animals; D017209:Apoptosis; D001400:Azurin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D001426:Bacterial Proteins; D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D001400:Azurin; C017167:cytochrome C(551)