Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes

Patricia M. Gaffney, Denise Imai, Deana L. Clifford, Majid Ghassemian, Roman Sasik, Aaron N. Chang, Timothy D. O'Brien, Judith Coppinger, Margarita Trejo, Eliezer Masliah, Linda Munson, Christina Sigurdson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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. These studies define a remarkably prevalent AA amyloidosis in island foxes with widespread systemic amyloid

Original languageEnglish (US)
Article numbere113765
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 26 2014

Fingerprint

amyloidosis
Amyloidosis
amyloid
Serum Amyloid A Protein
Amyloid
Islands
Proteomics
proteomics
blood serum
Peptides
Amino Acids
peptides
Complement C4
Kidney
Complement C3
Urocyon littoralis
Amyloid Plaques
Apolipoproteins E
amino acids
Fibrinogen

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Gaffney, P. M., Imai, D., Clifford, D. L., Ghassemian, M., Sasik, R., Chang, A. N., ... Sigurdson, C. (2014). Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes. PLoS One, 9(11), [e113765]. https://doi.org/10.1371/journal.pone.0113765

Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes. / Gaffney, Patricia M.; Imai, Denise; Clifford, Deana L.; Ghassemian, Majid; Sasik, Roman; Chang, Aaron N.; O'Brien, Timothy D.; Coppinger, Judith; Trejo, Margarita; Masliah, Eliezer; Munson, Linda; Sigurdson, Christina.

In: PLoS One, Vol. 9, No. 11, e113765, 26.11.2014.

Research output: Contribution to journalArticle

Gaffney, PM, Imai, D, Clifford, DL, Ghassemian, M, Sasik, R, Chang, AN, O'Brien, TD, Coppinger, J, Trejo, M, Masliah, E, Munson, L & Sigurdson, C 2014, 'Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes', PLoS One, vol. 9, no. 11, e113765. https://doi.org/10.1371/journal.pone.0113765
Gaffney, Patricia M. ; Imai, Denise ; Clifford, Deana L. ; Ghassemian, Majid ; Sasik, Roman ; Chang, Aaron N. ; O'Brien, Timothy D. ; Coppinger, Judith ; Trejo, Margarita ; Masliah, Eliezer ; Munson, Linda ; Sigurdson, Christina. / Proteomic analysis of highly prevalent amyloid a amyloidosis endemic to endangered Island foxes. In: PLoS One. 2014 ; Vol. 9, No. 11.
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