AMPD3 is involved in anthrax LeTx-induced macrophage cell death
Protein & Cell
; (12): 564-572, 2011.
Article
em En
| WPRIM
| ID: wpr-757065
Biblioteca responsável:
WPRO
ABSTRACT
The responses of macrophages to Bacillus anthracis infection are important for the survival of the host, since macrophages are required for the germination of B. anthracis spores in lymph nodes, and macrophage death exacerbates anthrax lethal toxin (LeTx)-induced organ collapse. To elucidate the mechanism of macrophage cell death induced by LeTx, we performed a genetic screen to search for genes associated with LeTx-induced macrophage cell death. RAW264.7 cells, a macrophage-like cell line sensitive to LeTx-induced death, were randomly mutated and LeTx-resistant mutant clones were selected. AMP deaminase 3 (AMPD3), an enzyme that converts AMP to IMP, was identified to be mutated in one of the resistant clones. The requirement of AMPD3 in LeTx-induced cell death of RAW 264.7 cells was confirmed by the restoration of LeTx sensitivity with ectopic reconstitution of AMPD3 expression. AMPD3 deficiency does not affect LeTx entering cells and the cleavage of mitogen-activated protein kinase kinase (MKK) by lethal factor inside cells, but does impair an unknown downstream event that is linked to cell death. Our data provides new information regarding LeTx-induced macrophage death and suggests that there is a key regulatory site downstream of or parallel to MKK cleavage that controls the cell death in LeTx-treated macrophages.
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Índice:
WPRIM
Assunto principal:
Patologia
/
Toxinas Bacterianas
/
Dados de Sequência Molecular
/
Sequência de Bases
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Linhagem Celular
/
Sobrevivência Celular
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Células Cultivadas
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Western Blotting
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Reação em Cadeia da Polimerase
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Morte Celular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2011
Tipo de documento:
Article