Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1: potential explanation for higher risk of type AA amyloidosis.
until further notice
Number of pages
SourceRheumatology, 47, 11, (2008), pp. 1651-1654
Article / Letter to editor
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SubjectEcological Microbiology; IGMD 2: Molecular gastro-enterology and hepatology; N4i 1: Pathogenesis and modulation of inflammation; N4i 2: Invasive mycoses and compromised host; NCMLS 1: Infection and autoimmunity; NCMLS 5: Membrane transport and intracellular motility; UMCN 4.1: Microbial pathogenesis and host defense; UMCN 5.1: Genetic defects of metabolism
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.
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