In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: Possible protection against amyloid fibril formation

T. Yamada, B. Kluve-Beckerman, J. J. Liepnieks, Merrill Benson

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Abstract

The effects of acid proteases on degradation of serum amyloid A protein (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), when incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited by an acid protease inhibitor, pepstatin. The degraded SAA molecules lacking nine or more amino-terminal residues, when exposed to in vitro fibril-forming conditions, failed to form Congo red positive precipitates and did not show amyloid fibril-like structure by electron microscopy. This suggests that the amino-terminal portion of SAA is essential for fibril formation. Cathepsin D, one of the lysosomal enzymes, also initiated degradation of rSAA1 at the amino-terminus. Cathepsin D immunoreactivity was detected in marginal areas of amyloid deposits in spleens from patients with reactive amyloidosis. These findings suggest that cathepsin D or similar acid proteases may be involved in SAA catabolism and may protect against amyloid formation.

Original languageEnglish (US)
Pages (from-to)570-574
Number of pages5
JournalScandinavian Journal of Immunology
Volume41
Issue number6
DOIs
StatePublished - 1995

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Serum Amyloid A Protein
Cathepsin D
Amyloid
Peptide Hydrolases
Acids
Spleen
Congo Red
Amyloid Plaques
Amyloidosis
Protease Inhibitors
Electron Microscopy
In Vitro Techniques
Enzymes

ASJC Scopus subject areas

  • Immunology

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In vitro degradation of serum amyloid A by cathepsin D and other acid proteases : Possible protection against amyloid fibril formation. / Yamada, T.; Kluve-Beckerman, B.; Liepnieks, J. J.; Benson, Merrill.

In: Scandinavian Journal of Immunology, Vol. 41, No. 6, 1995, p. 570-574.

Research output: Contribution to journalArticle

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