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Lipid-bound apolipoproteins in tyrosyl radical-oxidized HDL stabilize ABCA1 like lipid-free apolipoprotein A-I Hossain, Mohammad A.; Ngeth, Sereyrath; Chan, Teddy; Oda, Michael N.; Francis, Gordon A.
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.
Item Metadata
| Title |
Lipid-bound apolipoproteins in tyrosyl radical-oxidized HDL stabilize ABCA1 like lipid-free apolipoprotein A-I
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| Creator | |
| Contributor | |
| Publisher |
BioMed Central
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| Date Issued |
2012-01-16
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| Description |
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.
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| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2016-01-08
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
Attribution 4.0 International (CC BY 4.0)
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| DOI |
10.14288/1.0223226
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| URI | |
| Affiliation | |
| Citation |
BMC Biochemistry. 2012 Jan 16;13(1):1
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| Publisher DOI |
10.1186/1471-2091-13-1
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| Peer Review Status |
Reviewed
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| Scholarly Level |
Faculty
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| Copyright Holder |
Hossain et al; licensee BioMed Central Ltd.
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| Rights URI | |
| Aggregated Source Repository |
DSpace
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Rights
Attribution 4.0 International (CC BY 4.0)