ENDOSOMAL PROTEOLYSIS PRECEDES RICIN A-CHAIN TOXICITY IN MACROPHAGES

被引:22
|
作者
FIANI, ML [1 ]
BLUM, JS [1 ]
STAHL, PD [1 ]
机构
[1] WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110
关键词
D O I
10.1006/abbi.1993.1583
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ricin A-chain is delivered into macrophages via receptor-mediated endocytosis. We have found that following uptake via the mannose receptor, ricin A-chain is rapidly cleaved by endosomal proteases. Inhibition of endosomal protenses such as cathepsin D and B leads to the accumulation of toxin inside the cell. Inhibition of cathepsin D reduces ricin A-chain cytotoxicity, while blocking cathepsin B enhances cytotoxicity. Similar results were obtained using fibroblasts transfected with the mannose receptor. Our data strongly suggest that the activation or membrane translocation of ricin A-chain is dependent upon the action of specific proteases. © 1993 Academic Press, Inc.
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收藏
页码:225 / 230
页数:6
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