Abstract
Serum amyloid A (SAA) levels increase during acute and chronic inflammation and are mainly associated with high-density lipoprotein (HDL). In the present study, we investigated the effect of SAA on the composition, surface charge, particle size and antioxidant ability of HDL using recombinant human SAA (rhSAA) and HDL samples from patients with inflammation. We confirmed that rhSAA bound to HDL3 and released apolipoprotein A-I (apoA-I) from HDL without an apparent change in particle size. Forty-one patients were stratified into three groups based on serum SAA concentrations: Low (SAA ≤ 8 μg/ml), Middle (8 < SAA ≤ 100 μg/ml) and High (SAA > 100 μg/ml). The ratios of apoA-I to total protein mass, relative cholesterol content and negative charge of HDL samples obtained from patients with high SAA levels were lower than that for samples from patients with low SAA levels. Various particle sizes of HDL were observed in three groups regardless of serum SAA levels. Antioxidant ability of rhSAA, evaluated as the effect on the formation of conjugated diene in low-density lipoprotein (LDL) induced by oxidation using copper sulfate, was higher than that of apoA-I. Consistent with this result, reconstituted SAA-containing HDL (SAA-HDL) indicated higher antioxidant ability compared with normal HDL. Furthermore, HDL samples obtained from High SAA group patients also showed the highest antioxidant ability among the three groups. Consequently, SAA affects the composition and surface charge of HDL by displacement of apoA-I and enhances its antioxidant ability.
Highlights
Serum amyloid A (SAA) is one of the acute phase proteins predominantly produced in the liver during acute phase response (APR) to inflammatory stimulus such as infection, trauma, surgery and malignant tumour [1]
We examined the functional change of high-density lipoprotein (HDL), especially relative to its antioxidant ability, associated with the structural change, using reconstituted SAA-containing HDL (SAA-HDL) and HDL obtained from the patients with high SAA levels in serum
HDL remodelling induced by recombinant human SAA (rhSAA) To test the effect of SAA on HDL structure, rhSAA was incubated with normal HDL at a ratio similar to that in the APR state, and after ultracentrifugation, HDL fractions (Top) and protein fractions (Bottom) were analysed by SDS/PAGE and non-denaturing gel electrophoresis
Summary
Serum amyloid A (SAA) is one of the acute phase proteins predominantly produced in the liver during acute phase response (APR) to inflammatory stimulus such as infection, trauma, surgery and malignant tumour [1]. The physiological function of SAA has not been clearly determined yet. SAA, a polypeptide composed by 104 amino acids, consists of four isoforms, SAA1–SAA4 [4]. SAA3, a minor isoform considered a pseudogene, was recently found to be expressed as a fusion protein with SAA2 in humans [6]. SAA4 is a constitutive isoform that represents more than 90 % of total SAA under normal physiological conditions [7]; the level does not change dramatically in response to inflammation [8]. SAA circulates in plasma as a component of one of the lipoproteins, high-density lipoprotein (HDL) [10]
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