Tan Yian Kim, Kusuma Caroline M, St John Lena J, Vu Hao A, Alibek Kenneth, Wu Aiguo
Molecular and Microbiology Department, College of Sciences, George Mason University, Manassas, VA 22010, USA.
Biochem Biophys Res Commun. 2009 Feb 6;379(2):293-7. doi: 10.1016/j.bbrc.2008.12.048. Epub 2008 Dec 25.
Autophagy is an evolutionary conserved intracellular process whereby cells break down long-lived proteins and organelles. Accumulating evidences suggest increasing physiological significance of autophagy in pathogenesis of infectious diseases. Anthrax lethal toxin (LT) exerts its influence on numerous cells and herein, we report a novel effect of LT-induced autophagy on mammalian cells. Several autophagy biochemical markers including LC3-II conversion, increased punctuate distribution of GFP-LC3 and development of acidic vesicular organelles (AVO) were detected in cells treated with LT. Analysis of individual LT component revealed a moderate increase in LC3-II conversion for protective antigen-treated cells, whereas the LC3-II level in lethal factor-treated cells remained unchanged. In addition, our preliminary findings suggest a protective role of autophagy in LT intoxication as autophagy inhibition resulted in accelerated cell death. This study presents a hitherto undescribed effect of LT-induced autophagy on cells and provides the groundwork for future studies on the implication of autophagy in anthrax pathogenesis.
自噬是一种进化保守的细胞内过程,通过该过程细胞分解长寿命蛋白质和细胞器。越来越多的证据表明自噬在传染病发病机制中的生理意义日益增加。炭疽致死毒素(LT)对多种细胞产生影响,在此我们报告LT诱导的自噬对哺乳动物细胞的一种新作用。在用LT处理的细胞中检测到了几种自噬生化标志物,包括LC3-II转化、GFP-LC3点状分布增加以及酸性囊泡细胞器(AVO)的形成。对LT各个组分的分析显示,经保护性抗原处理的细胞中LC3-II转化有适度增加,而经致死因子处理的细胞中LC3-II水平保持不变。此外,我们的初步研究结果表明自噬在LT中毒中具有保护作用,因为自噬抑制导致细胞死亡加速。本研究展示了LT诱导的自噬对细胞迄今未描述的作用,并为未来关于自噬在炭疽发病机制中的意义的研究奠定了基础。