title: Lipid-bound apolipoproteins in tyrosyl radical-oxidized HDL stabilize ABCA1 like lipid-free apolipoprotein A-I.
abstract: 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.
authors.affiliation: Department of Medicine, UBC James Hogg Research Centre, Heart and Lung Institute, St, Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Hossain
authors.forename: Sereyrath
authors.initials: S
authors.lastname: Ngeth
authors.forename: Teddy
authors.initials: T
authors.lastname: Chan
authors.forename: Michael N
authors.initials: MN
authors.lastname: Oda
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Francis
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004765:Enteropeptidase / Q000737:chemistry; D004951:Esterification; D015870:Gene Expression; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D014443:Tyrosine; D002784:Cholesterol; D004765:Enteropeptidase; D002154:Calpain