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

Hilst, Jeroen Van der; Yamada, Toshiyuki; Camp, Huub J. M. Op den; Meer, J.W.M. van der; Drenth, J.P.H.; Simon, Anna

doi:10.1093/rheumatology/ken371

Cited by 40 publications

(29 citation statements)

References 33 publications

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“…Further confirmation was recently provided by the Nijmegen group of investigators (38), who demonstrated that susceptibility to MMP-1 degradation is highly dependent on SAA1 genotype. Significantly, SAA1.1 but not SAA1.5 is largely cleaved by MMP-1 between residues 57 and 58, and this proteolytic event is related to the presence of Ala 57 , which belongs to both SAA1.1 and SAA1.3 isoforms but is absent in SAA1.5 (38). Therefore, these data seem to be in agreement with the accelerated clearance of SAA1.1 and SAA1.3 compared with SAA1.5 and point to the possibility that susceptibility to N-terminal cleavage at residue 57 might be related to the higher risk of development of AA associated with these genotypes.…”

Section: Prevalence Of Aa Amyloidosis In Rheumatic Diseasesmentioning

confidence: 74%

“…Subsequently, in vitro studies confirmed that human SAAs and AA amyloid fibrils are susceptible to proteolytic cleavage by MMPs, generating fragments of different sizes (37). Further confirmation was recently provided by the Nijmegen group of investigators (38), who demonstrated that susceptibility to MMP-1 degradation is highly dependent on SAA1 genotype. Significantly, SAA1.1 but not SAA1.5 is largely cleaved by MMP-1 between residues 57 and 58, and this proteolytic event is related to the presence of Ala 57 , which belongs to both SAA1.1 and SAA1.3 isoforms but is absent in SAA1.5 (38).…”

Section: Prevalence Of Aa Amyloidosis In Rheumatic Diseasesmentioning

confidence: 86%

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Susceptibility to AA amyloidosis in rheumatic diseases: A critical overview

Obici¹,

Raimondi²,

Lavatelli³

et al. 2009

Arthritis & Rheumatism

103

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Section: Prevalence Of Aa Amyloidosis In Rheumatic Diseasesmentioning

confidence: 74%

Section: Prevalence Of Aa Amyloidosis In Rheumatic Diseasesmentioning

confidence: 86%

Susceptibility to AA amyloidosis in rheumatic diseases: A critical overview

Obici¹,

Raimondi²,

Lavatelli³

et al. 2009

Arthritis & Rheumatism

103

View full text Add to dashboard Cite

“…In humans, SAA-1 is also the precursor of reactive amyloid fibrils in type AA amyloidosis, a condition caused by deposition of insoluble fibrillar amyloid proteins (a degraded N-terminus fragment of SAA) in the extracellular space in many organs and tissues (Merlini and Bellotti 2003). Several alleles have been discovered with different susceptibilities to amyloid formation, e.g., SAA1.1 is more susceptible than SAA1.5 (van der Hilst et al 2008). …”

Section: Saa-1mentioning

confidence: 99%

Plasma biomarkers of mouse aging

Ding

Kopchick

2010

AGE

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Normal aging is accompanied by a series of physiological changes such as gray hair, cataracts, reduced immunity, and increased susceptibility to disease. To identify novel biomarkers of normal aging, we analyzed plasma proteins of male mice longitudinally from 2 to 19 months of age. Plasma proteins were analyzed by two-dimensional gel electrophoresis and identified using mass spectrometry (MS), MS/MS and liquid chromatography MS/MS. We found that many plasma proteins exist as multiple isoforms with different masses and/or charges. Thirty-nine protein spots (corresponding to six distinct proteins) have been identified, 13 of which exhibited significant changes with age. For example, several proteins increased significantly during aging including one isoform of transthyretin, two isoforms of haptoglobin, and three isoforms of immunoglobulin kappa chain. Conversely, several proteins decreased significantly during aging including peroxiredoxin-2, serum amyloid protein A-1, and five isoforms of albumin. Identification of these proteins provides new biomarkers of normal aging in mice. If validated in humans, these biomarkers may facilitate therapeutic interventions to identify premature aging, delay aging, and/or improve healthspan of the elderly.

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“…The SAA1.1 (α) isoform is more susceptible to cleavage by MMP-1 than SAA1.5 (β), resulting in a higher production of the 1-57 fragments from SAA1 . 1 (α) [29] .…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Type 1 Gene Polymorphism in Egyptian Children with Familial Mediterranean Fever

Wilson¹,

Abou-Elalla

Zakaria

et al. 2016

Pathobiology

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Background: Since spontaneous inflammation is an important contributor to familial Mediterranean fever (FMF), genetic variants mediating inflammation are of interest. We investigated gene variants in the acute-phase serum amyloid A type 1 (SAA1), a sensitive marker of inflammatory activity, and their association with susceptibility and severity of FMF. Methods: The genotypes of 2 single-nucleotide polymorphisms within exon 3 of SAA1 (2995C/T and 3010C/T) were determined in 105 Egyptian children with FMF and in 125 controls by polymerase chain reaction-restriction fragment length polymorphism. Genotyping of the causative MEFV mutations was performed by reverse hybridization. Results: The M694I mutation was the most frequent allele (42.8%), followed by V726A (18.6%), M680I (17.1%), E148Q (11.9%) and M694V (9.0%). The frequency of the SAA1 α, β and γ alleles was not significantly different between FMF patients and controls. The genotype frequency of SAA1 α/α was higher in patients than in healthy subjects (21.0 vs. 14.4%) although it did not reach statistical significance. The clinical manifestations including age at disease onset, number of FMF attacks, colchicine dose and severity score were not related to genotypes of SAA1. However, M694V mutation and female gender were significantly associated with severity. Conclusion: The genetic polymorphism of SAA1 is not associated with susceptibility and severity of FMF in Egyptian children.

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

Abstract: 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.

Cited by 40 publications

References 33 publications

Susceptibility to AA amyloidosis in rheumatic diseases: A critical overview

Susceptibility to AA amyloidosis in rheumatic diseases: A critical overview

Plasma biomarkers of mouse aging

Serum Amyloid A Type 1 Gene Polymorphism in Egyptian Children with Familial Mediterranean Fever

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