Back to Search
Start Over
ATP-binding Cassette Transporter A1 Mediates Cellular Secretion of α-Tocopherol
- Source :
- Journal of Biological Chemistry. 276:39898-39902
- Publication Year :
- 2001
- Publisher :
- Elsevier BV, 2001.
-
Abstract
- Alpha-tocopherol (alpha-TOH) is associated with plasma lipoproteins and accumulates in cell membranes throughout the body, suggesting that lipoproteins play a role in transporting alpha-TOH between tissues. Here we show that secretion of alpha-TOH from cultured cells is mediated in part by ABCA1, an ATP-binding cassette protein that transports cellular cholesterol and phospholipids to lipid-poor high density lipoprotein (HDL) apolipoproteins such as apoA-I. Treatment of human fibroblasts and murine RAW264 macrophages with cholesterol and/or 8-bromo-cyclic AMP, which induces ABCA1 expression, enhanced apoA-I-mediated alpha-TOH efflux. ApoA-I lacked the ability to remove alpha-TOH from Tangier disease fibroblasts that have a nonfunctional ABCA1. BHK cells that lack an active ABCA1 pathway markedly increased secretion of alpha-TOH to apoA-I when forced to express ABCA1. ABCA1 also mediated a fraction of the alpha-TOH efflux promoted by lipid-containing HDL particles, indicating that HDL promotes alpha-TOH efflux by both ABCA1-dependent and -independent processes. Exposing apoA-I to ABCA1-expressing cells did not enhance its ability to remove alpha-TOH from cells lacking ABCA1, consistent with this transporter participating directly in the translocation of alpha-TOH to apolipoproteins. These studies provide evidence that ABCA1 mediates secretion of cellular alpha-TOH into the HDL metabolic pathway, a process that may facilitate vitamin transport between tissues and influence lipid oxidation.
- Subjects :
- alpha-Tocopherol
8-Bromo Cyclic Adenosine Monophosphate
Biological Transport, Active
Biochemistry
Mice
chemistry.chemical_compound
High-density lipoprotein
Tangier disease
Lipid oxidation
Vitamin transport
Cricetinae
Cyclic AMP
polycyclic compounds
medicine
Animals
Humans
Secretion
Molecular Biology
Tangier Disease
Apolipoprotein A-I
biology
Cholesterol
Macrophages
nutritional and metabolic diseases
hemic and immune systems
Cell Biology
Fibroblasts
medicine.disease
Recombinant Proteins
Cell biology
ATP Binding Cassette Transporter 1
chemistry
ABCA1
biology.protein
ATP-Binding Cassette Transporters
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 276
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....6de0bcb6e6f6011c57126f0eb20ff6bf