Endosomal Proteolysis Precedes Ricin A-Chain Toxicity in Macrophages

M. L. Fiani, Janice Blum, P. D. Stahl

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume307
Issue number2
DOIs
StatePublished - Dec 1993
Externally publishedYes

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Proteolysis
Ricin
Macrophages
Toxicity
Cathepsin B
Cathepsin D
Cytotoxicity
Peptide Hydrolases
Fibroblasts
Endocytosis
Chemical activation
Membranes
mannose receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Biochemistry

Cite this

Endosomal Proteolysis Precedes Ricin A-Chain Toxicity in Macrophages. / Fiani, M. L.; Blum, Janice; Stahl, P. D.

In: Archives of Biochemistry and Biophysics, Vol. 307, No. 2, 12.1993, p. 225-230.

Research output: Contribution to journalArticle

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