TY - JOUR
T1 - Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes
AU - Gaffney, Patricia M.
AU - Imai, Denise M.
AU - Clifford, Deana L.
AU - Ghassemian, Majid
AU - Sasik, Roman
AU - Chang, Aaron N.
AU - O'Brien, Timothy D.
AU - Coppinger, Judith
AU - Trejo, Margarita
AU - Masliah, Eliezer
AU - Munson, Linda
AU - Sigurdson, Christina
N1 - Publisher Copyright:
©2014 Gaffney et al.
PY - 2014/11/26
Y1 - 2014/11/26
N2 - Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates.
AB - Amyloid A (AA) amyloidosis is a debilitating, often fatal, systemic amyloid disease associated with chronic inflammation and persistently elevated serum amyloid A (SAA). Elevated SAA is necessary but not sufficient to cause disease and the risk factors for AA amyloidosis remain poorly understood. Here we identify an extraordinarily high prevalence of AA amyloidosis (34%) in a genetically isolated population of island foxes (Urocyon littoralis) with concurrent chronic inflammatory diseases. Amyloid deposits were most common in kidney (76%), spleen (58%), oral cavity (45%), and vasculature (44%) and were composed of unbranching, 10 nm in diameter fibrils. Peptide sequencing by mass spectrometry revealed that SAA peptides were dominant in amyloid-laden kidney, together with high levels of apolipoprotein E, apolipoprotein A-IV, fibrinogen-α chain, and complement C3 and C4 (false discovery rate ≤0.05). Reassembled peptide sequences showed island fox SAA as an 111 amino acid protein, most similar to dog and artic fox, with 5 unique amino acid variants among carnivores. SAA peptides extended to the last two C-terminal amino acids in 5 of 9 samples, indicating that near full length SAA was often present in amyloid aggregates.
UR - http://www.scopus.com/inward/record.url?scp=84956608536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84956608536&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0113765
DO - 10.1371/journal.pone.0113765
M3 - Article
C2 - 25429466
AN - SCOPUS:84956608536
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 11
M1 - e113765
ER -