Rat tissues express serum amyloid A protein-related mRNAs.

Abstract

Serum amyloid A (SAA) is a small (12 kDa) acute-phase apoprotein of high density lipoprotein found in mammals. It is also the precursor to amyloid protein A, the main protein constituent of fibrils found in amyloidosis secondary to chronic or recurrent inflammation-e.g., rheumatoid arthritis. However, rats do not develop amyloidosis and SAA is not an apoprotein of rat high density lipoprotein; thus rats appear to be an exception in regard to expression of SAA genes. We report here that rats do have representatives of the SAA gene family and express two distinct SAA mRNAs. Moreover, the pattern of genes expressed among tissues, and their induction by inflammatory agents, is similar to that of related mouse genes. RNA from various tissues of normal and injured rats was examined by RNA blot hybridization with SAA cDNA and complementary RNA probes for the three murine SAA genes. A SAA mRNA of '400 nucleotides related to mouse SAA1 and SAA2 mRNAs reached a high level in liver 24 hr after injection of bacterial lipopolysaccharide. No extrahepatic tissues were found to express the SAA1/SAA2-related mRNA. Turpentine induced two hepatic SAA1/SAA2-related mRNAs of "400 and -"500 nucleotides in length. Liver SAA,/SAA2-related mRNA hybrid selected and translated in a wheat germ protein-synthesizing system, from lipopolysaccharide-and turpentine-injected rats, produced a single protein with an estimated molecular mass of 8 kDa. This rat liver SAA-related mRNA appears to lack a highly conserved coding region for portions of two amphipathic helical domains and the joining sequence. An mRNA related to mouse SAA3 was found expressed at a high level in lung after lipopolysaccharide but not following turpentine injection. This mRNA was also expressed at high levels in ileum and large intestine of control rats and was not found in the liver of control or challenged rats. These observations show that the SAA gene family is present and expressed in rats and that its expression is found under situations similar to those found in mice. This lends support for the importance of the SAA gene family in the response to injury by vertebrates.A complex series of systemic and metabolic changes occur in vertebrates in response to injury or infection. These reactions are collectively termed the acute-phase response. Conspicuous among these events is the rise in concentration of certain plasma proteins of hepatic origin termed acute-phase proteins (1). Serum amyloid A (SAA) is a family of apolipoproteins found mainly associated with high density lipoprotein (HDL) (2, 3). Members of this family are acute-phase proteins (1,4,5). In addition, part of the SAA is a component of amyloid deposits associated with inflammatory disease. The major protein of these deposits is amyloid A protein (AA), comprising the NH2-terminal 76 residues of the circulating precursor SAA (6, 7). However, rats do not develop amyloidosis and no SAA has been found in rat HDL following injury. The apparent absence ofexpression in the rat has been puzzling because of the...

Serum amyloid A (SAA3) produced by rabbit synovial fibroblasts treated with phorbol esters or interleukin 1 induces synthesis of collagenase and is neutralized with specific antiserum.

“…Expression of SAA mRNAs has been described in tissues of animals injected with LPS or turpentine. These include lung, heart, spleen, intestines, and kidney in mice (23), and ileum, lung, and large intestine in rats (24), as well as numerous hamster tissues (19). In both the hamster and rat, the SAA3 mRNA is found only in extrahepatic tissues, leading the authors to conclude that SAA3 may be expressed abundantly at local nonhepatic sites of inflammation and tissue injury (19,23,24).…”

“…These include lung, heart, spleen, intestines, and kidney in mice (23), and ileum, lung, and large intestine in rats (24), as well as numerous hamster tissues (19). In both the hamster and rat, the SAA3 mRNA is found only in extrahepatic tissues, leading the authors to conclude that SAA3 may be expressed abundantly at local nonhepatic sites of inflammation and tissue injury (19,23,24). Our observations extend these findings by demonstrating that cultured fibroblasts of nonhepatic origin express increased amounts of SAA3 in response to two additional inflammatory mediators, PMA and IL-1.…”

Expression of Serum Amyloid A, in Normal, Dysplastic, and Neoplastic Human Colonic Mucosa: Implication for a Role in Colonic Tumorigenesis

“…The SAA probe was prepared from pGEM transcription vector that contained a 110-bp sequence of mouse SAA1 cDNA (p125) (Meek and Benditt 1989). This nucleotide sequence encompasses a domain coding for amino acid residues 30-66 that is highly conserved among species and is highly homologous with human SAA genes, as described previously .…”

Widespread Expression of Serum Amyloid A in Histologically Normal Human Tissues: Predominant Localization to the Epithelium

“…SAA probe was prepared from pGEM transcription vector that contained a 110-bp sequence of mouse SAA1 cDNA (p125) (Meek and Benditt 1989a). This nucleotide sequence encompasses a domain coding for amino acid residues 30-66 that is highly conserved among species.…”