Serum amyloid A protein forms a complex with a fragment of Apolipoprotein A-I in the domestic blue fox: a protective mechanism against AA amyloidosis?

Abstract

The spontaneous occurrence of protein AA-type of amyloidosis varies among animal species. As reactive AA-type of amyloidosis has never been detected in the blue fox, we obtained acute phase sera to search for amyloid-protective elements. The purified SAA fraction was characterized by mass and sequence analyses to disclose any unique domains in the amino acid sequence. The data revealed an SAA protein with heterogeneities in several positions, and showed the typical insertion between positions 69 and 70. By comparing the amino acid sequence with that from other mammals, no unique sequence could be observed. However, a C-terminal fragment of apolipoprotein A-I (ApoA-I) was found attached to the SAA. The amino acid sequence of the ApoA-I fragment revealed a partially blocked and ragged N-terminus. A comparison of the amino acid sequence of ApoA-I with that from the dog showed that the ApoA-I fragment started about position 190, had an intact C-terminus, and showed an identical sequence in all positions, except one. Based on the data, we suggest an interaction of the C-terminal fragment of ApoA-I with the SAA protein that inhibits the AA fibrillogenesis in the blue fox.

Systemic AA amyloidosis in the red fox (Vulpes vulpes)

“…SDS PAGE analysis of dissolved fibrils and of material from the major retarded peak after gel filtration, showed distinct bands with apparent molecular weights of around 10–12 kDa [Fig. (D)], which is compatible with the previously described 111‐residue SAA from Island and Blue fox . Western blot with two different antisera identified the protein band materials as protein AA [Fig.…”

“… Sequence alignment of SAA from human ( Homo sapiens , Uniprot ID: P0DJI8), island fox ( Urocyon littorals ), dog ( Canis lupus familiaris , UniProt ID: P19708), Red fox ( Vulpes vulpes ) and Blue fox ( Alopex lagopus ) . The location of the α‐helices determined by X‐ray crystallography is indicated by blue bars.…”

“…As expected, Red fox SAA has high sequence similarities to SAA from other species. Since the Blue fox may be resistant to the development of AA amyloidosis, the sequence differences between these two species are of interest. Three of the four positions in which the amino acid sequence between the Red fox and Blue fox SAA differ are located in the loops between helices, as judged from sequence alignment to human SAA, for which a 3D structure is available .…”

“…AA amyloidosis occurs spontaneously in many mammalian and avian species, but the prevalence varies considerably even between subgroups of the same species. In dogs, AA amyloidosis is common, while the disease has never been described in the Blue fox ( Alopex lagopus ), and was not found in Gray foxes ( Urocyon cinereoargenteus ; n = 401) . In contrast, foxes that live on the Channel Islands off the Californian coast ( Urocyon littoralis ) suffer from a high prevalence of AA amyloidosis, possibly due to genetic variations in the SAA gene …”

“…In dogs, AA amyloidosis is common, while the disease has never been described in the Blue fox (Alopex lagopus), and was not found in Gray foxes (Urocyon cinereoargenteus; n 5 401). 8,9 In contrast, foxes that live on the Channel Islands off the Californian coast (Urocyon littoralis) suffer from a high prevalence of AA amyloidosis, possibly due to genetic variations in the SAA gene. 9 Herein, we report on the identification of AA amyloidosis in the Red fox (Vulpes vulpes).…”