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
来源：
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 1993年 / 307卷 / 02期
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.
引用
收藏
页码：225 / 230
页数：6
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