Lipid-bound apolipoproteins in tyrosyl radical-oxidized HDL stabilize ABCA1 like lipid-free apolipoprotein A-I.

TitleLipid-bound apolipoproteins in tyrosyl radical-oxidized HDL stabilize ABCA1 like lipid-free apolipoprotein A-I.
Publication TypeJournal Article
Year of Publication2012
AuthorsHossain, MA, Ngeth, S, Chan, T, Oda, MN, Francis, GA
JournalBMC Biochem
Date Published2012
KeywordsApolipoprotein A-I, ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters, Calpain, Cell Membrane, Cells, Cultured, Cholesterol, Enteropeptidase, Esterification, Gene Expression, Humans, Lipoproteins, HDL, Oxidation-Reduction, Protein Binding, Protein Stability, Protein Transport, Proteolysis, Tyrosine

BACKGROUND: ATP-binding cassette transporter A1 (ABCA1) mediates the lipidation of exchangeable apolipoproteins, the rate-limiting step in the formation of high density lipoproteins (HDL). We previously demonstrated that HDL oxidized ex vivo by peroxidase-generated tyrosyl radical (tyrosylated HDL, tyrHDL) increases the availability of cellular cholesterol for efflux and reduces the development of atherosclerosis when administered to apolipoprotein E-deficient mice as compared to treatment with control HDL.RESULTS: In the current study we determined that tyrHDL requires functional ABCA1 for this enhanced activity. Like lipid-free apolipoprotein A-I (apoA-I), tyrHDL increases total and cell surface ABCA1, inhibits calpain-dependent and -independent proteolysis of ABCA1, and can be bound by cell surface ABCA1 in human skin fibroblasts. Additionally, tyrHDL apoproteins are susceptible to digestion by enteropeptidase like lipid-free apoA-I, but unlike lipid-bound apoA-I on HDL, which is resistant to proteolysis.CONCLUSIONS: These results provide the first evidence that lipid-bound apolipoproteins on the surface of spherical HDL particles can behave like lipid-free apoA-I to increase ABCA1 protein levels and activity.

Alternate JournalBMC Biochem.
PubMed ID22248050
PubMed Central IDPMC3292454
Grant ListMOP-12660 / / Canadian Institutes of Health Research / Canada