Most studies of experimental amyloid A protein (AA) amyloidosis in mice have been performed in type A mice with BALB/c as the prototype. In these mice the products of two genes, SAA1 and SAA2, are the major apo-SAA isoforms on high density lipoprotein (HDL). Of these two isoforms, that differ at nine amino acids, only apo-SAA2 is rapidly cleared and deposited as amyloid fibrils. No mouse strain has ever been shown to be completely resistant to amyloid induction. We have found the CE/J mouse strain to be exceedingly resistant to amyloidogenesis. Data indicate that this resistance is not due to a lack of apo-SAA synthesis but rather resides in the unique apo-SAA isoform in this strain. CE/J mice have a single major apo-SAA isoform (pI 6.15) the product of a single gene. This is a hybrid molecule with features of both apo-SAA1 and apo-SAA2, differing from the latter at only six amino acids. When CD studies were performed to explore the structural relationship of this isoform to apo-SAA1 and apo-SAA2, we found that when bound to heparan sulfate proteoglycan the CE/J pI 6.15 isoform fails to undergo the beta-sheet folding typical for apo-SAA2. This evidence suggests that the folding effect of heparan sulfate proteoglycan on apo-SAA2 is important in amyloid formation.
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J Neuroinflammation
May 2018
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Largo "E. Meneghetti" 2, 35131, Padua, Italy.
Background: Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1β (IL-1β), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1β release is promoted by ATP acting at the purinergic P2X receptor (P2XR) in cells primed with toll-like receptor (TLR) ligands.
View Article and Find Full Text PDFLab Invest
December 2000
Department of Biochemistry, University of Kentucky, Lexington, USA.
Amyloid A (AA) amyloid deposition in mice is dependent upon isoform-specific effects of the serum amyloid A (SAA) protein. In type A mice, SAA1.1 and SAA2.
View Article and Find Full Text PDFJ Biol Chem
September 1993
Department of Medicine, University of Kentucky Medical Center, Lexington 40536.
Most studies of experimental amyloid A protein (AA) amyloidosis in mice have been performed in type A mice with BALB/c as the prototype. In these mice the products of two genes, SAA1 and SAA2, are the major apo-SAA isoforms on high density lipoprotein (HDL). Of these two isoforms, that differ at nine amino acids, only apo-SAA2 is rapidly cleared and deposited as amyloid fibrils.
View Article and Find Full Text PDFClin Physiol Biochem
August 1993
Laboratoire de Biochimie, CHU La Rabta, Tunis, Tunisia.
The purpose of this study was to determine the effects of antimony treatment on the altered lipoprotein system of four young Tunisians with visceral Leishmaniasis and to further investigate possible relationships between acute phase proteins (C-reactive protein and apolipoprotein SAA)-known to be increased in this disease-and lipid or apolipoprotein (apo) parameters measured before and throughout the treatment. A marked improvement of all investigated parameters was already observed after the first cure: the lecithin-cholesterol acyltransferase activity was the only parameter remaining deficient even at the end of the second cure. Statistical analysis reveals a significant inverse relationship between changes in C-reactive protein and changes in the plasma ratio of esterified to total cholesterol (r = -0.
View Article and Find Full Text PDFBiochem J
May 1992
Department of Medicine, University of Kentucky Medical Center, Lexington 40536.
Four serum amyloid A protein (SAA) genes and two gene products, apo-SAA1 and apo-SAA2 were identified in BALB/c mice (type A). SJL/J mice (type B) are thought to be defective in apo-SAA2 expression. A unique variant of mouse apo-SAA was identified in SJL/J mice by isoelectric-focusing analysis of high-density lipoprotein from endotoxin-treated mice.
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