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dc.contributor.authorHa, S. D.zh_CN
dc.contributor.authorNg, D.zh_CN
dc.contributor.authorLamothe, J.zh_CN
dc.contributor.authorValvano, M. A.zh_CN
dc.contributor.authorHan, J. H.zh_CN
dc.contributor.authorKim, S. O.zh_CN
dc.contributor.author韩家淮zh_CN
dc.date.accessioned2013-12-12T02:24:43Z
dc.date.available2013-12-12T02:24:43Z
dc.date.issued2007zh_CN
dc.identifier.citationJournal of Biological Chemistry,282(36):26275-26283zh_CN
dc.identifier.issn0021-9258zh_CN
dc.identifier.otherISI:000249239600032zh_CN
dc.identifier.urihttps://dspace.xmu.edu.cn/handle/2288/65827
dc.description.abstractAnthrax 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.zh_CN
dc.language.isoen_USzh_CN
dc.subjectNF-KAPPA-Bzh_CN
dc.subjectBACILLUS-ANTHRACISzh_CN
dc.subjectMESSENGER-RNAzh_CN
dc.subjectINHALATIONAL ANTHRAXzh_CN
dc.subjectKINASE-KINASEzh_CN
dc.subjectHOST RESPONSEzh_CN
dc.subjectTNF-ALPHAzh_CN
dc.subjectSUSCEPTIBILITYzh_CN
dc.subjectSPORESzh_CN
dc.subjectPATHOGENESISzh_CN
dc.titleMitochondrial proteins bnip3 and Bnip3L are involved in anthrax lethal toxin-induced macrophage cell deathzh_CN
dc.typeArticlezh_CN


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