Increased susceptibility of serum amyloid A 1.1 to degradation by MMP-1: potential explanation for higher risk of type AA amyloidosis.

Autor:	van der Hilst JC; Department of General Internal Medicine (463), Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands. j.vanderhilst@aig.umcn.nl, Yamada T, Op den Camp HJ, van der Meer JW, Drenth JP, Simon A
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2008 Nov; Vol. 47 (11), pp. 1651-4. Date of Electronic Publication: 2008 Sep 24.
DOI:	10.1093/rheumatology/ken371
Abstrakt:	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.
Databáze:	MEDLINE
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