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炭疽芽孢杆菌致死因子的细胞毒性活性受到白三烯A4水解酶和金属肽酶抑制剂的抑制。

The cytotoxic activity of Bacillus anthracis lethal factor is inhibited by leukotriene A4 hydrolase and metallopeptidase inhibitors.

作者信息

Menard A, Papini E, Mock M, Montecucco C

机构信息

Centro CNR Biomembrane, Università di Padova, Italy.

出版信息

Biochem J. 1996 Dec 1;320 ( Pt 2)(Pt 2):687-91. doi: 10.1042/bj3200687.

Abstract

The lethal factor of Bacillus anthracis is central to the pathogenesis of anthrax. Its mechanism of action is still unknown. Recently, on the basis of sequence similarities, we suggested that lethal factor might act similarly to leukotriene A4 hydrolase (LTA4), a bifunctional enzyme also endowed with a metallopeptidase activity. Here we show that some inhibitors of the LTA4 hydrolase and metallopeptidase activities of LTA4 hydrolase also affect the cytotoxicity of the anthrax lethal factor on macrophage cell lines, without interfering with the ability of the lethal factor to enter cells. These results support the proposal that anthrax lethal factor might display in the cytosol of intoxicated cells a peptidase activity similar to that of LTA4 hydrolase.

摘要

炭疽芽孢杆菌致死因子是炭疽病发病机制的核心。其作用机制尚不清楚。最近,基于序列相似性,我们提出致死因子的作用方式可能与白三烯A4水解酶(LTA4)相似,LTA4是一种也具有金属肽酶活性的双功能酶。在此我们表明,一些LTA4水解酶的LTA4水解酶和金属肽酶活性抑制剂也会影响炭疽致死因子对巨噬细胞系的细胞毒性,而不干扰致死因子进入细胞的能力。这些结果支持了以下观点:炭疽致死因子可能在受感染细胞的胞质溶胶中表现出与LTA4水解酶相似的肽酶活性。

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