TY - JOUR
T1 - Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1
T2 - Potential explanation for higher risk of type AA amyloidosis
AU - van der Hilst, J. C. H.
AU - Yamada, T.
AU - op den Camp, H. J. M.
AU - van der Meer, J. W. M.
AU - Drenth, J. P. H.
AU - Simon, A.
PY - 2008
Y1 - 2008
N2 - Objective. Genetic polymorphisms in serum amyloid A (SAA) have been shown to substantially influence the risk of developing type AA amyloidosis. Recently, a role for MMP-1 has been suggested in the pathogenesis of AA amyloidosis. Therefore, we investigated if the SAA1 isotypes are differentially degraded by MMP-1. Methods. Degradation of different SAA isotypes by MMP-1 was assessed by immunoblotting. MALDI-TOF mass spectrometry was used to identify degradation fragments. Results. We found that SAA1.5 is more resistant to degradation by MMP-1 than SAA1.1. This difference is caused by the capacity of MMP-1 to cleave at the site of the polymorphism at position 57. Conclusion. These results may explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons with a SAA1.5 genotype. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
AB - Objective. Genetic polymorphisms in serum amyloid A (SAA) have been shown to substantially influence the risk of developing type AA amyloidosis. Recently, a role for MMP-1 has been suggested in the pathogenesis of AA amyloidosis. Therefore, we investigated if the SAA1 isotypes are differentially degraded by MMP-1. Methods. Degradation of different SAA isotypes by MMP-1 was assessed by immunoblotting. MALDI-TOF mass spectrometry was used to identify degradation fragments. Results. We found that SAA1.5 is more resistant to degradation by MMP-1 than SAA1.1. This difference is caused by the capacity of MMP-1 to cleave at the site of the polymorphism at position 57. Conclusion. These results may explain the higher risk of amyloidosis in patients with a SAA1.1/1.1 genotype vs SAA1.5/1.5 or SAA1.1/1.5 genotype. In addition, the impaired degradation of SAA1.5 by MMP-1 could also explain the higher serum SAA concentrations in persons with a SAA1.5 genotype. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=54449084360&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/18815155
U2 - https://doi.org/10.1093/rheumatology/ken371
DO - https://doi.org/10.1093/rheumatology/ken371
M3 - Article
C2 - 18815155
SN - 1462-0324
VL - 47
SP - 1651
EP - 1654
JO - Rheumatology
JF - Rheumatology
IS - 11
ER -