Lipid-free apolipoprotein A-I and discoidal reconstituted high-density lipoproteins differentially inhibit glucose-induced oxidative stress in human macrophages

Tabet, F., Lambert, G., Cuesta Torres, L.F., Hou, L., Sotirchos, I., Touyz, R.M. , Jenkins, A.J., Barter, P.J. and Rye, K.A. (2011) Lipid-free apolipoprotein A-I and discoidal reconstituted high-density lipoproteins differentially inhibit glucose-induced oxidative stress in human macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), pp. 1192-1200. (doi: 10.1161/ATVBAHA.110.222000)

Full text not currently available from Enlighten.

Abstract

<b>Objective—</b>The goal of this study was to investigate the mechanisms by which apolipoprotein (apo) A-I, in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins ([A-I]rHDL), inhibits high-glucose–induced redox signaling in human monocyte-derived macrophages (HMDM).<p></p> <b>Methods and Results—</b>HMDM were incubated under normal (5.8 mmol/L) or high-glucose (25 mmol/L) conditions with native high-density lipoproteins (HDL) lipid-free apoA-I from normal subjects and from subjects with type 2 diabetes (T2D) or (A-I)rHDL. Superoxide (O2−) production was measured using dihydroethidium fluorescence. NADPH oxidase activity was assessed using lucigenin-derived chemiluminescence and a cyotochrome c assay. p47phox translocation to the plasma membrane, Nox2, superoxide dismutase 1 (SOD1), and SOD2 mRNA and protein levels were determined by real-time polymerase chain reaction and Western blotting. Native HDL induced a time-dependent inhibition of O2− generation in HMDM incubated with 25 mmol/L glucose. Lipid-free apoA-I and (A-I)rHDL increased SOD1 and SOD2 levels and attenuated 25 mmol/L glucose-mediated increases in cellular O2−, NADPH oxidase activity, p47 translocation, and Nox2 expression. Lipid-free apoA-I mediated its effects on Nox2, SOD1, and SOD2 via ABCA1. (A-I)rHDL-mediated effects were via ABCG1 and scavenger receptor BI. Lipid-free apoA-I from subjects with T2D inhibited reactive oxygen species generation less efficiently than normal apoA-I.<p></p> <b>Conclusion—</b>Native HDL, lipid-free apoA-I and (A-I)rHDL inhibit high-glucose–induced redox signaling in HMDM. The antioxidant properties of apoA-I are attenuated in T2D.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Tabet, F., Lambert, G., Cuesta Torres, L.F., Hou, L., Sotirchos, I., Touyz, R.M., Jenkins, A.J., Barter, P.J., and Rye, K.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:17 February 2011

University Staff: Request a correction | Enlighten Editors: Update this record