Induction of Adrenal Scavenger Receptor BI and Increased High Density Lipoprotein-Cholesteryl Ether Uptake by in Vivo Inhibition of Hepatic Lipase

• Published in: The Journal of biological chemistry 1998-11, Vol.273 (48), p.32038-32041
• Main Authors: Bruggen, Delfina Vieira-van, Kalkman, Ina, van Gent, Teus, van Tol, Arie, Jansen, Hans
• Format: Article
• Language: English
• Subjects: Adrenal Glands - drug effects; Adrenal Glands - metabolism; Adrenocorticotropic Hormone - pharmacology; Animals; Biological Transport; CD36 Antigens - biosynthesis; CD36 Antigens - genetics; Cholesterol, HDL - metabolism; DNA Primers; Ethers - metabolism; Humans; Kinetics; Lipoprotein Lipase - antagonists & inhibitors; Male; Membrane Proteins; Mice; Polymerase Chain Reaction; Rats; Rats, Wistar; Receptors, Immunologic; Receptors, Lipoprotein - biosynthesis; Receptors, Lipoprotein - genetics; Receptors, Scavenger; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Scavenger Receptors, Class B; Time Factors; Transcription, Genetic; Up-Regulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.48.32038

Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have both been implicated in high density lipoprotein (HDL)-cholesteryl ester uptake in cholesterol-utilizing tissues. Inactivation of HL by gene-directed targeting in mice results in up-regulation of SR-BI expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall, A. R. (1996) J. Biol. Chem. 271, 21001–21004). The net effect on HDL-cholesteryl ester uptake is not known. We determined the impact of acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in the adrenal gland. Rat HDL was isolated from rats in which HL activity had been inhibited for 1 h. The rats were studied under basal conditions (not ACTH-treated) and after previous treatment with ACTH for 6 days (ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering of adrenal HL activity in both conditions which were maintained for at least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased adrenal SR-BI mRNA (5.2-fold) and mass (1.6-fold) within 4 h. HL inhibition resulted in 41% and 14% more adrenal accumulation of human HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH treatment increased total adrenal HL activity from 3.7 ± 0.5 milliunits to 34.0 ± 17.2 milliunits, as well as adrenal SR-BI mRNA from 2.9 ± 0.7 arbitrary units (A.U.) to 86.8 ± 41.1 A.U. and SR-BI mass from 7.7 ± 1.8 A.U. to 63.16 ± 46.7 A.U. The human HDL-[3H]CEth uptake by adrenals was also significantly increased from 0.58 ± 0.11% of injected dose to 7.24 ± 1.58% of injected dose. Inhibition of adrenal HL activity did not result in further induction of SR-BI expression and did not affect human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression may be influenced by changes in HL activity. HL activity is not needed for the SR-BI-mediated HDL-cholesteryl ester uptake by rat adrenal glands.