Amyloid protein SAA is an apoprotein of mouse plasma high density lipoprotein.

Benditt, Earl P.; Eriksen, Nils; Rc, Hanson

doi:10.1073/pnas.76.8.4092

Cited by 122 publications

(70 citation statements)

References 34 publications

(19 reference statements)

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“…The amyloid A fibril protein, AA, may be produced by proteolytic cleavage (4) of the SAAL polypeptide synthesized by hepatocytes and transported in serum amyloid A to sites of amyloid deposition such as the kidney (8,9,13). Our findings support this model.…”

Section: And 5) (22)supporting

confidence: 80%

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Induction of hepatic synthesis of serum amyloid A protein and actin.

Morrow¹,

Stearman²,

Peltzman³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

164

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Major changes in the mRNA population of murine liver occur after administration of bacterial lipopolysaccharide, an agent that causes increases in the concentrations of acutephase serum proteins. The mRNA for one of these, serum amyloid A, is increased at least 500-fold compared to the normal level. It becomes one of the most abundant hepatic mRNAs, and serum amyloid A synthesis comprises about 2.5% of total hepatic protein synthesis in the acute-phase response. Its synthesis is tissue-specific in that amyloid A mRNA was not detected in the kidney, an important site of amyloid fibril accumulation. The protein synthesized in largest amount by acute-phase liver tissue in culture is cytoplasmic actin. Its relative rate ofsynthesis is increased about 5-fold compared to the normal tissue; that of serum albumin is decreased to about one-third ofits normal rate. The concentration of mRNA for serum albumin is decreased by a similar amount. Starting with induced liver RNA, we have constructed a recombinant plasmid containing most ofthe DNA sequence encoding the serum amyloid A polypeptide.

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Section: And 5) (22)supporting

confidence: 80%

“…Rabbit antiserum to murine amyloid A protein was kindly provided by J. D. Sipe (1,8,10). Lipoproteins were removed (13) and IgG was purified (14). Purified human platelet actin was generously given by I. M. Herman and T. D. Pollard (15) (Fig.…”

Section: Methodsmentioning

confidence: 99%

Induction of hepatic synthesis of serum amyloid A protein and actin.

Morrow¹,

Stearman²,

Peltzman³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

164

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“…Defibrinated pooled serum was prepared 24 h post-injection. The HDL 3 was purified by serial ultracentrifugation according to the method of Benditt et al [22]. Purified HDL 3 lipoproteins were obtained at the top of the KBr density gradient of 1.21 g/ml.…”

Section: Methodsmentioning

confidence: 99%

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

et al. 1997

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1997;45:354-360 Reactive AA amyloidosis can be induced in mice in a model of sustained inflammation following daily casein subcutaneous injections. However, the development of AA amyloidosis is known to vary in different strains of mice. The C57BL/6 strain is susceptible to the development of amyloidosis while the A/J strain is resistant. The degradation of purified serum amyloid A (SAA) protein by human monocytes as well as by mouse macrophages has been shown. The resistance/susceptibility of different mouse strains to the development of systemic amyloidosis may therefore be related to a difference in the ability of macrophages to degrade SAA. The authors have used bone marrow-derived macrophage cell lines obtained from susceptible C57BL/6 (ANA-1) and resistant A/J (A/J 10) mouse strains to compare their ability to degrade HDL-SAA in vitro. Cells were incubated with HDL-SAA for up to 72 h and the culture medium was analysed by SDS-PAGE to determine the rate of SAA degradation by the macrophages. The A/J 10 cells (resistant) were found to initiate a constant HDL-SAA degradation promptly whereas ANA-1 cells (susceptible) showed an intermittent block in the degradation of the precursor. Activation of macrophages by lipopolysaccharide (LPS) or interferon-g (IFN-g) hampered the precursor degradation suggesting that the activation process may favour extracellular accumulation of the precursor leading to a partial degradation and fibril formation.

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“…SAA is a nonspecific acute phase protein, with a dynamic range of 1 to >3,000 mg/L in humans, synthesized by hepatocytes under the control of proinflammatory cytokines (3). The deposition of AAtype amyloid in the viscera, connective tissue, and blood vessel walls damages tissue structure and function, with the kidney as the major target organ (4).…”

Section: Rs | Disease Modelmentioning

confidence: 99%

Pathogenetic mechanisms of amyloid A amyloidosis

Simons

Al‐Shawi

Ellmerich

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Systemic amyloid A (AA) amyloidosis is a serious complication of chronic inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited extracellularly as insoluble amyloid fibrils that damage tissue structure and function. Clinical AA amyloidosis is typically preceded by many years of active inflammation before presenting, most commonly with renal involvement. Using dose-dependent, doxycycline-inducible transgenic expression of SAA in mice, we show that AA amyloid deposition can occur independently of inflammation and that the time before amyloid deposition is determined by the circulating SAA concentration. High level SAA expression induced amyloidosis in all mice after a short, slightly variable delay. SAA was rapidly incorporated into amyloid, acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest SAA overexpression occasionally produced amyloidosis after long delays and primed most mice for explosive amyloidosis when SAA production subsequently increased. Endogenous priming and bulk amyloid deposition are thus separable events, each sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with restoration of normal SAA production after doxycycline withdrawal. Reinduction of SAA overproduction revealed that, following amyloid regression, all mice were primed, especially for rapid glomerular amyloid deposition leading to renal failure, closely resembling the rapid onset of renal failure in clinical AA amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis rarely involves the heart, but amyloidotic SAA transgenic mice consistently had minor cardiac amyloid deposits, enabling us to extend to the heart the demonstrable efficacy of our unique antibody therapy for elimination of visceral amyloid.

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Amyloid protein SAA is an apoprotein of mouse plasma high density lipoprotein.

Cited by 122 publications

References 34 publications

Induction of hepatic synthesis of serum amyloid A protein and actin.

Induction of hepatic synthesis of serum amyloid A protein and actin.

Degradation of Amyloid A Precursor Protein SAA by Macrophage Cell Lines Obtained from Amyloid Resistant and Susceptible Strains of Mice

Pathogenetic mechanisms of amyloid A amyloidosis

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