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	Mitochondrial proteins bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell death
	Ha, S. D. ; Ng, D. ; Lamothe, J. ; Valvano, M. A. ; Han, J. H. ; Kim, S. O. ; Han JH(韩家淮)
	2007
关键词	NF-KAPPA-B BACILLUS-ANTHRACIS MESSENGER-RNA INHALATIONAL ANTHRAX KINASE-KINASE HOST RESPONSE TNF-ALPHA SUSCEPTIBILITY SPORES PATHOGENESIS
英文摘要	Anthrax lethal toxin (LeTx) induces rapid cell death of RAW246.7 macrophages. We recently found that a small population of these macrophages is spontaneously and temporally refractory to LeTx-induced cytotoxicity. Analysis of genomewide transcripts of a resistant clone before and after regaining LeTx sensitivity revealed that a reduction of two closely related mitochondrial proteins, Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (Bnip3) and Bnip3-like (Bnip3L), correlates with LeTx resistance. Down-regulation of Bnip3 and Bnip3L was also found in "toxin-induced resistance" whereby sublethal doses of LeTx induce resistance to subsequent exposure to cytolytic toxin doses. The role of Bnip3 and Bnip3L in LeTx-induced cell death was confirmed by showing that overexpression of either Bnip3 or Bnip3L rendered the resistant cells susceptible to LeTx, whereas down-regulation of Bnip3 and Bnip3L in wildtype macrophages conferred resistance. The down-regulation of Bnip3 and Bnip3L mRNAs by LeTx occurred at both transcriptional and mRNA stability levels. Inhibition of the p38 pathway by lethal factor was responsible for the destabilization of Bnip3/Bnip3L mRNAs as confirmed by showing that p38 inhibitors stabilized Bnip3 and Bnip3L mRNAs and conferred resistance to LeTx cytotoxicity. Therefore, Bnip3/Bnip3L play a crucial role in LeTx-induced cytotoxicity, and down-regulation of Bnip3/Bnip3L is a mechanism of spontaneous or toxin-induced resistance of macrophages.
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65827]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Ha, S. D.,Ng, D.,Lamothe, J.,et al. Mitochondrial proteins bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell death[J],2007.
APA	Ha, S. D..,Ng, D..,Lamothe, J..,Valvano, M. A..,Han, J. H..,...&韩家淮.(2007).Mitochondrial proteins bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell death..
MLA	Ha, S. D.,et al."Mitochondrial proteins bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell death".(2007).

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