Gomaraschi, M; Putt, WE; Pozzi, S; Iametti, S; Barbiroli, A; Bonomi, F; ... Calabresi, L; + view all Gomaraschi, M; Putt, WE; Pozzi, S; Iametti, S; Barbiroli, A; Bonomi, F; Favari, E; Bernini, F; Franceschini, G; Talmud, PJ; Calabresi, L; - view fewer (2010) Structure and function of the apoA-IV T347S and Q360H common variants. BIOCHEM BIOPH RES CO , 393 (1) 126 - 130. 10.1016/j.bbrc.2010.01.099.
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Human apolipoprotein A-IV (apoA-IV) is involved in chylomicron assembly and secretion, and in reverse cholesterol transport. Several apoA-IV isoforms exist, the most common in Caucasian populations being apoA-IV-1a (T347S) and apoA-IV-2 (Q360H). The objective of the present study was to investigate the impact of these common aminoacid substitutions on the ability of apoA-IV to bind lipids, to promote cell cholesterol efflux via ABCA1, and to maintain endothelial homeostasis. Recombinant forms of wild-type apoA-IV, apoA-IV Q360H, and apoA-IV T347S were produced in Escherichia coli. ApoA-IV Q360H and apoA-IV T347S showed a slightly higher alpha-helical content compared to wild-type apoA-IV, and associated with phospholipids faster than wild-type apoA-IV. The capacity to promote ABCA1-mediated cholesterol efflux was significantly greater for the apoA-IV T347S than the other apoA-IV isoforms. No differences were observed in the ability of apoA-IV isoforms to inhibit the production of VCAM-1 and IL-6 in TNF alpha-stimulated endothelial cells. In conclusion, the apoA-IV T347S common variant has increased lipid binding properties and cholesterol efflux capacity, while the apoA-IV Q360H variant has only slightly increased lipid binding properties. The two common aminoacid substitutions have no effect on the ability of apoA-IV to maintain endothelial homeostasis. (C) 2010 Elsevier Inc. All rights reserved.
|Title:||Structure and function of the apoA-IV T347S and Q360H common variants|
|Keywords:||Apolipoprotein A-IV, High density lipoproteins, Cellular cholesterol efflux, Vascular endothelium, APOLIPOPROTEIN-A-IV, HIGH-DENSITY-LIPOPROTEINS, CHOLESTEROL EFFLUX, ENDOTHELIAL-CELLS, N-TERMINI, C-TERMINI, PLASMA, BINDING, PROTEIN, CONFORMATION|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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