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

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.

• Authors: T Yamada, B Kluve-Beckerman, J J Liepnieks, M D Benson
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 41 Issue 6 Pg. 570-4 (Jun 1995) ISSN: 0300-9475 [Print] England
• PMID: 7770727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amyloid
• Serum Amyloid A Protein
• Aspartic Acid Endopeptidases
• Cathepsin D

Topics

• Amyloid (metabolism)
• Aspartic Acid Endopeptidases (metabolism)
• Cathepsin D (metabolism)
• Electrophoresis, Polyacrylamide Gel
• Humans
• Kidney (enzymology)
• Liver (enzymology)
• Serum Amyloid A Protein (metabolism)
• Spleen (enzymology)