scholarly journals Differential plasma clearance of murine acute-phase serum amyloid A proteins SAA1 and SAA2

1997 ◽  
Vol 322 (2) ◽  
pp. 663-669 ◽  
Author(s):  
Barbara KLUVE-BECKERMAN ◽  
Toshiyuki YAMADA ◽  
Joyce HARDWICK ◽  
Juris J. LIEPNIEKS ◽  
Merrill D. BENSON
Keyword(s):  
Acute Phase ◽  
Half Life ◽  
Plasma Clearance ◽  
Serum Amyloid A ◽  
Tissue Injury ◽  
Density Lipoprotein ◽  
Serum Amyloid ◽  
Acute Phase Reactants ◽  
Amyloid A ◽  
Potential Factor

Serum amyloid A (SAA) proteins SAA1 and SAA2 are prominent acute-phase reactants which circulate in association with the high-density-lipoprotein (HDL) fraction of plasma. Plasma levels of SAA1 and SAA2 increase dramatically, by as much as 1000-fold, within 24 h of tissue injury and then rapidly decrease with cessation of the inflammatory stimulus, suggesting that SAA clearance and/or catabolism is important to the re-establishment of homoeostasis. In this context, aberrant SAA catabolism has long been considered a potential factor in the pathogenesis of reactive amyloidosis. To initiate studies aimed at understanding the differential regulation of SAA metabolism, we have produced 35S-labelled murine SAA1 and SAA2 in Escherichia coli, bound them individually to HDL, and then compared the plasma-clearance characteristics of SAA1 and SAA2 under normal and acute-phase conditions. When bound to normal HDL, SAA2 [half-life (t½) = 30 min] was cleared significantly faster than SAA1 (t½ = 75 min). Clearance of SAA1 and SAA2 was significantly slower when each was bound to acute-phase HDL as opposed to normal HDL, when clearance rates were determined in acute-phase mice versus normal mice, and when normal HDL was remodelled to contain both recombinant isotypes rather than just one of the isotypes. Thus it appears that an increased amount of SAA on HDL, or possibly the combined presence of both isotypes on HDL, is associated with a prolongation in the plasma half-life of SAA.

scholarly journals Heparan Sulfate Dissociates Serum Amyloid A (SAA) from Acute-phase High-density Lipoprotein, Promoting SAA Aggregation

2012 ◽  
Vol 287 (30) ◽  
pp. 25669-25677 ◽  
Author(s):  
Fredrik Noborn ◽  
John B. Ancsin ◽  
Wimal Ubhayasekera ◽  
Robert Kisilevsky ◽  
Jin-Ping Li
Keyword(s):  
High Density Lipoprotein ◽  
Heparan Sulfate ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Density Lipoprotein ◽  
High Density ◽  
Serum Amyloid ◽  
Amyloid A

scholarly journals Phosphorylation of human serum amyloid A protein by protein kinase C

1988 ◽  
Vol 255 (1) ◽  
pp. 29-34 ◽  
Author(s):  
A E Nel ◽  
M C De Beer ◽  
E G Shephard ◽  
A F Strachan ◽  
M L Vandenplas ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Density Lipoprotein ◽  
Acute Phase Reactant ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Kinase C ◽  
Serum Amyloid A Protein

Monokine-induced hepatic secretion of serum amyloid A protein (apo-SAA), an acute-phase reactant, is followed by rapid association with high-density lipoprotein (HDL) in plasma. Plasma clearance of apo-SAA is more rapid than any of the other HDL apolipoproteins. It has been shown that, of the acute-phase HDL3 apolipoproteins, apo-SAA preferentially associates with neutrophil membranes. HDL apolipoproteins have been shown to activate protein kinase C in endothelial cells. We therefore investigated potential phosphorylation of HDL3 apolipoproteins by protein kinase C. Apo-SAA was the only apolipoprotein phosphorylated (Km = 12 mM). Phosphorylation of the apo-SAA-containing HDL3 particle was selective for the more basic isoforms of apo-SAA (pI 7.0, 7.4, 7.5 and 8.0), with more acidic isoforms being phosphorylated when delipidated acute-phase apolipoproteins were used as substrate. However, phosphorylation was not in itself responsible for the establishment of the apo-SAA isoforms.

Abstract 388: Impact of Individual Acute Phase Serum Amyloid A Isoforms on HDL Metabolism in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Maria C De Beer ◽  
Myung-Hee Kim ◽  
Joanne M Wroblewski ◽  
Richard C Charnigo ◽  
Ailing Ji ◽  
...  
Keyword(s):  
Acute Phase ◽  
Plasma Clearance ◽  
Serum Amyloid A ◽  
Biological Activities ◽  
Acute Phase Reactant ◽  
Serum Amyloid ◽  
Minor Role ◽  
Clearance Rates ◽  
Amyloid A ◽  
Significant Difference

The acute phase reactant serum amyloid A (SAA) is an HDL apolipoprotein that exhibits biological activities as a pro-inflammatory mediator, but its physiological function(s) are poorly understood. Possible functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are also unclear. Mice deficient in either SAA1.1 or SAA2.1 were used to investigate SAA isoform plasma clearance rates and effects on HDL structure, composition and apolipoprotein catabolism. The absence of either isoform did not affect the size of the normally enlarged HDL found in acute phase wild type mice, and did not result in significant changes in HDL lipid composition. Plasma clearance rates of normal and acute phase HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCR’s) of apoA-I, apoA-II and SAA were distinct, indicating that neither normal nor acute phase particles are cleared as intact particles. No significant difference was found between the FCR’s of SAA1.1 and SAA2.1 in acute phase mice, suggesting that the selective deposition of SAA1.1 observed in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. In the absence of the HDL receptor SR-BI, the clearance rate of SAA was reduced by about 30% and remained significantly greater compared to that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA clearance. These studies contribute to our understanding of the metabolism of SAA and its effects on acute phase HDL composition and catabolism.

scholarly journals Adenoviral expression of murine serum amyloid A proteins to study amyloid fibrillogenesis

1998 ◽  
Vol 332 (3) ◽  
pp. 721-728 ◽  
Author(s):  
Mark S. KINDY ◽  
Amy R. KING ◽  
Jin YU ◽  
Connie GERARDOT ◽  
Joel WHITLEY ◽  
...  
Keyword(s):  
Acute Phase ◽  
Half Life ◽  
Serum Amyloid A ◽  
Amyloid Fibrils ◽  
Serum Amyloid ◽  
Vector System ◽  
High Density Lipoproteins ◽  
Secondary Amyloidosis ◽  
Amyloid A ◽  
J Protein

Serum amyloid A (SAA) proteins are one of the most inducible acute-phase reactants and are precursors of secondary amyloidosis. In the mouse, SAA1 and SAA2 are induced in approximately equal quantities in response to amyloid induction models. These two isotypes differ in only 9 of 103 amino acid residues; however, only SAA2 is selectively deposited into amyloid fibrils. SAA expression in the CE/J mouse species is an exception in that gene duplication did not occur and the CE/J variant is a hybrid molecule sharing features of SAA1 and SAA2. However, even though it is more closely related to SAA2 it is not deposited as amyloid fibrils. We have developed an adenoviral vector system to overexpress SAA proteins in cell culture to determine the ability of these proteins to form amyloid fibrils, and to study the structural features in relation to amyloid formation. Both the SAA2 and CE/J SAA proteins were synthesized in large quantities and purified to homogeneity. Electron microscopic analysis of the SAA proteins revealed that the SAA2 protein was capable of forming amyloid fibrils, whereas the CE/J SAA was incapable. Radiolabelled SAAs were associated with normal or acute-phase high-density lipoproteins (HDLs); we examined them for their clearance from the circulation. In normal mice, SAA2 had a half-life of 70 min and CE/J SAA had a half-life of 120 min; however, in amyloid mice 50% of the SAA2 cleared in 55 min, compared with 135 min for the CE/J protein. When the SAA proteins were associated with acute-phase HDLs, SAA2 clearance was decreased to 60 min in normal mice compared with 30 min in amyloidogenic mice. Both normal and acute-phase HDLs were capable of depositing SAA2 into preformed amyloid fibrils, whereas the CE/J protein did not become associated with amyloid fibrils. This established approach opens the doors for large-scale SAA production and for the examination of specific amino acids involved in the fibrillogenic capability of the SAA2 molecule in vitro and in vivo.

scholarly journals The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality

2015 ◽  
Vol 396 (6-7) ◽  
pp. 573-583 ◽  
Author(s):  
Nicole Prüfer ◽  
Burkhard Kleuser ◽  
Markus van der Giet
Keyword(s):  
High Density Lipoprotein ◽  
Acute Phase ◽  
Serum Amyloid A ◽  
Biological Activities ◽  
Density Lipoprotein ◽  
High Density ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Hdl Function ◽  
Sphingosine 1 Phosphate

Abstract The high-density lipoprotein (HDL) is one of the most important endogenous cardiovascular protective markers. HDL is an attractive target in the search for new pharmaceutical therapies and in the prevention of cardiovascular events. Some of HDL’s anti-atherogenic properties are related to the signaling molecule sphingosine-1-phosphate (S1P), which plays an important role in vascular homeostasis. However, for different patient populations it seems more complicated. Significant changes in HDL’s protective potency are reduced under pathologic conditions and HDL might even serve as a proatherogenic particle. Under uremic conditions especially there is a change in the compounds associated with HDL. S1P is reduced and acute phase proteins such as serum amyloid A (SAA) are found to be elevated in HDL. The conversion of HDL in inflammation changes the functional properties of HDL. High amounts of SAA are associated with the occurrence of cardiovascular diseases such as atherosclerosis. SAA has potent pro-atherogenic properties, which may have impact on HDL’s biological functions, including cholesterol efflux capacity, antioxidative and anti-inflammatory activities. This review focuses on two molecules that affect the functionality of HDL. The balance between functional and dysfunctional HDL is disturbed after the loss of the protective sphingolipid molecule S1P and the accumulation of the acute-phase protein SAA. This review also summarizes the biological activities of lipid-free and lipid-bound SAA and its impact on HDL function.

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