Abstract |
17beta-estradiol (E2) fatty acyl esters naturally incorporate into high-density lipoprotein (HDL). The objective was to elucidate mechanisms involved in HDL-associated E2 cellular uptake and to determine the intracellular distribution of E2 and its fatty acyl esters (E2-FAE) after uptake. [3H]E2 or [3H] cholesterol was incubated with human serum for 24 h to allow for fatty acyl esterification. Total-HDL containing [3H]E2-FAE or [3H] cholesterol esters was isolated by sequential density ultracentrifugation and then incubated with Fu5AH rat hepatoma cells for various time points. Cellular uptake was determined by intracellular radioactivity as a percentage of total radioactivity. Chemical inhibition of scavenger receptor class B, type I and low-density lipoprotein ( LDL) receptor competition assays were performed to determine cellular uptake mechanisms. Compared to HDL-[3H] cholesterol, cellular uptake of HDL-[3H]E2 occurred at an initially rapid rate. SR-BI inhibition resulted in a decrease in HDL-E2 uptake and LDL impaired this uptake in a concentration-dependent manner. Accordingly, pretreatment of cells with BLT-1 combined with LDL addition significantly attenuated HDL-E2 uptake. HDL-E2-FAE was hydrolyzed into free E2 with the maximum at 24 h. Fu5AH cells facilitate HDL-E2 uptake by at least SR-BI and LDL receptor pathways and intracellular hydrolysis of E2-FAE into free E2 ensues.
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Authors | Robert M Badeau, Jari Metso, Matti J Tikkanen, Matti Jauhiainen |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1771
Issue 10
Pg. 1329-34
(Oct 2007)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 17905649
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD36 Antigens
- Esters
- Lipoproteins, HDL
- Receptors, LDL
- Estradiol
- Cholesterol
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Topics |
- Animals
- CD36 Antigens
(chemistry, metabolism)
- Carcinoma, Hepatocellular
(metabolism)
- Cell Line
- Cell Line, Tumor
- Cholesterol
(metabolism)
- Esters
(chemistry)
- Estradiol
(metabolism)
- Humans
- Lipoproteins, HDL
(metabolism)
- Models, Biological
- Rats
- Receptors, LDL
(metabolism)
- Ultracentrifugation
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