A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice

Liang, Jun-shan; Elliott-Bryant, Rosemary; Hajri, Tahar; Sipe, Jean D.; Cathcart, Edgar S.

doi:10.1016/s0005-2760(98)00102-7

Cited by 16 publications

(16 citation statements)

References 24 publications

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“…The first 16 residues of murine SAA2.1 and SAA1.1 are as follows: SAA2.1 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) GFFSFVHEAFQGAGDM SAA1.1 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) GFFSFIGEAFQGAGDM The differences in sequences relative to SAA2.1 are bold. Macrophage CEH activity is not significantly affected by the ingestion of RBC membrane fragments (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…In the mouse, the acute-phase isoforms of SAA are 103 residues long and are remarkably similar in sequence, being 91% homologous (5) and differing from each other by only nine amino acids. Most past functional studies have examined mixtures of these two isoforms, and there are relatively few studies (10) comparing the functional properties of these isoforms individually.…”

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confidence: 99%

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Promoting export of macrophage cholesterol

Tam

Flexman

Hulme

et al. 2002

Journal of Lipid Research

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We show that murine macrophages that have ingested cell membranes as a source of cholesterol exhibit a marked increase in acyl-CoA:cholesterol acyl tranferase (ACAT) activity. Exposure of these macrophages to acutephase high-density lipoprotein (HDL) results in a marked reduction of ACAT and enhancement of cholesteryl ester hydrolase (CEH) activities, phenomena not seen with native HDL. These complementary but opposite effects of acutephase HDL on the two enzyme systems that regulate the balance between esterified (storage) cholesterol and unesterified (transportable) cholesterol are shown to reside with serum amyloid A (SAA) 2.1, an acute-phase apolipoprotein of HDL whose plasma concentration increases 500-to 1,000-fold within 24 h of acute tissue injury. Mild trypsin treatment of acute-phase HDL almost completely abolishes the apoliporotein-mediated effects on the cholesteryl ester cycle in cholesterol-laden macrophages. The physiological effect of SAA2.1 on macrophage cholesterol is to shift it into a transportable state enhancing its rate of export, which we confirm in tissue culture and in vivo. The export process is shown to be coupled to the ATP binding cassette transport system. Our findings integrate previous isolated observations about SAA into the sphere of cholesterol transport, establish a function for a major acute-phase protein, and offer a novel approach to mobilizing macrophage cholesterol at sites of atherogenesis.-Shui Pang Tam, Alana Flexman, Jennifer Hulme, and Robert Kisilevsky. Promoting export of macrophage cholesterol: the physiological role of a major acute-phase protein, serum amyloid A 2.1. J. Lipid Res.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Promoting export of macrophage cholesterol

Tam

Flexman

Hulme

et al. 2002

Journal of Lipid Research

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“…The murine SAA2.2 cDNA was cloned into a pET21-a(ϩ) vector between the NdeI and BamHI sites and transformed into Escherichia coli strain BL21 (DE3) pLysS-competent cells as described (17). Cells were lysed in 2-amino-2-hydroxymethyl-1,3-propanediol (Tris) buffer (20 mM, pH 8.2) by three consecutive freezing-thawing cycles, and the lysate was added gradually to buffer A (Tris buffer͞6 M urea) and concentrated by ultrafiltration before loading onto a DEAE anion-exchange column (Sigma).…”

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confidence: 99%

Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channel

Wang

Lashuel

Walz

et al. 2002

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

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Serum amyloid A (SAA) is a small apolipoprotein that binds to high-density lipoproteins in the serum. Although SAA seems to play a role in host defense and lipid transport and metabolism, its specific functions have not been defined. Despite the growing implications that SAA plays a role in the pathology of various diseases, a high-resolution structure of SAA is lacking because of limited solubility in the high-density lipoprotein-free form. In this study, complementary methods including glutaraldehyde cross-linking, size-exclusion chromatography, and sedimentationvelocity analytical ultracentrifugation were used to show that murine SAA2.2 in aqueous solution exists in a monomer-hexamer equilibrium. Electron microscopy of hexameric SAA2.2 revealed that the subunits are arranged in a ring forming a putative central channel. Limited trypsin proteolysis and mass spectrometry analysis identified a significantly protease-resistant SAA2.2 region comprising residues 39 -86. The isolated 39 -86 SAA2.2 fragment did not hexamerize, suggesting that part of the N terminus is involved in SAA2.2 hexamer formation. Circular-dichroism spectrum deconvolution and secondary-structure prediction suggest that SAA2.2 contains Ϸ50% of its residues in ␣-helical conformation and <10% in ␤-structure. These findings are consistent with the recent discovery that human SAA1.1 forms a membrane channel and have important implications for understanding the 3D structure, multiple functions, and pathological roles of this highly conserved protein.S erum amyloid A (SAA) proteins are a family of apolipoproteins found predominantly associated with high-density lipoprotein (HDL) in plasma (1), with different isoforms being unequally expressed constitutively and in response to inflammatory stimuli (2). Although synthesized primarily in the liver, extrahepatic tissue͞cellular expression of SAA has been widely documented (3). SAA has been linked to functions related to inflammation, pathogen defense, HDL metabolism, and cholesterol transport and thereby has been implicated (3) in several pathological conditions including atherosclerosis, rheumatoid arthritis, Alzheimer's disease, and cancer.SAA is known best for its role during the acute phase response to an inflammatory stimulus such as infection, tissue injury, and trauma (2). During active inflammation the concentration of SAA in plasma can increase up to 1,000-fold within 24 h (4). It is believed that persistently high levels of SAA during chronic inflammation may contribute to the occasional development of the potentially fatal disease reactive amyloidosis [amyloid A (AA) amyloidosis] (5). In AA amyloidosis, AA, an N-terminal (1-76) fragment of SAA (6), frequently is found to form amyloid deposits in the liver, kidney, and spleen. However, the presence, in vivo, of full-length SAA in amyloid deposits (7) and the ability of various SAA isoforms to form fibrils in vitro (8-10) suggest that proteolytic cleavage may not be a prerequisite for AA deposition but rather a postdeposition event. Of the thre...

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“…by repeated injections of casein, LPS, or silver nitrate) and should represent an amyloidogenic isotype. Amyloid resistant mouse strains were found to have a non-amyloidogenic acute phase SAA (Gonnerman et al, 1995;Liang et al, 1998). Rats were shown not to form acute phase SAA and AA-amyloid at all (Ren et al, 1999;Yu et al, 2000).…”

Section: Fibrillogenesis and The Amyloid Enhancing Factor (Aef)mentioning

confidence: 99%

Protein folding pathology in domestic animals

Gruys

2004

J. Zheijang Univ.-Sci.

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Fibrillar proteins form structural elements of cells and the extracellular matrix. Pathological lesions of fibrillar microanatomical structures, or secondary fibrillar changes in globular proteins are well known. A special group concerns histologically amorphous deposits, amyloid. The major characteristics of amyloid are: apple green birefringence after Congo red staining of histological sections, and non-branching 7−10 nm thick fibrils on electron microscopy revealing a high content of cross beta pleated sheets. About 25 different types of amyloid have been characterised. In animals, AA-amyloid is the most frequent type. Other types of amyloid in animals represent: AIAPP (in cats), AApoAI, AApoAII, localised AL-amyloid, amyloid in odontogenic or mammary tumors and amyloid in the brain. In old dogs Aβ and in sheep APrP sc -amyloid can be encountered. AA-amyloidosis is a systemic disorder with a precursor in blood, acute phase serum amyloid A (SAA). In chronic inflammatory processes AA-amyloid can be deposited. A rapid crystallization of SAA to amyloid fibrils on small beta-sheeted fragments, the 'amyloid enhancing factor' (AEF), is known and the AEF has been shown to penetrate the enteric barrier. Amyloid fibrils can aggregate from various precursor proteins in vitro in particular at acidic pH and when proteolytic fragments are formed. Molecular chaperones influence this process. Tissue data point to amyloid fibrillogenesis in lysosomes and near cell surfaces. A comparison can be made of the fibrillogenesis in prion diseases and in enhanced AA-amyloidosis. In the reactive form, acute phase SAA is the supply of the precursor protein, whereas in the prion diseases, cell membrane proteins form a structural source. Aβ-amyloid in brain tissue of aged dogs showing signs of dementia forms a canine counterpart of senile dementia of the Alzheimer type (ccSDAT) in man. Misfolded proteins remain potential food hazards. Developments concerning prevention of amyloidogenesis and therapy of amyloid deposits are shortly commented.

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A unique amyloidogenic apolipoprotein serum amyloid A (apoSAA) isoform expressed by the amyloid resistant CE/J mouse strain exhibits higher affinity for macrophages than apoSAA1 and apoSAA2 expressed by amyloid susceptible CBA/J mice

Cited by 16 publications

References 24 publications

Promoting export of macrophage cholesterol

Promoting export of macrophage cholesterol

Murine apolipoprotein serum amyloid A in solution forms a hexamer containing a central channel

Protein folding pathology in domestic animals

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