Open Access Highly Accessed Research article

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

Mohammad A Hossain1, Sereyrath Ngeth1, Teddy Chan1, Michael N Oda2 and Gordon A Francis1*

Author Affiliations

1 Department of Medicine, UBC James Hogg Research Centre, Heart and Lung Institute, St. Paul's Hospital, Vancouver, British Columbia, Canada V6Z 1Y6

2 Children's Hospital Oakland Research Institute, Oakland, CA, USA 94609

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BMC Biochemistry 2012, 13:1  doi:10.1186/1471-2091-13-1

Published: 16 January 2012



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.


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.


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.