In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: possible protection against amyloid fibril formation.
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.
Yamada
T
T
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Kluve-Beckerman
B
B
Liepnieks
J J
JJ
Benson
M D
MD
D000682:Amyloid / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D013154:Spleen / Q000201:enzymology
D000682:Amyloid; D000685:Serum Amyloid A Protein; D016282:Aspartic Acid Endopeptidases; D002402:Cathepsin D