Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase.
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.
Vieira-van Bruggen
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D
Department of Biochemistry, Cardiovascular Research Institute Erasmus University Rotterdam (COEUR), 3000 DR Rotterdam, The Netherlands.
Kalkman
I
I
van Gent
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T
van Tol
A
A
Jansen
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H
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics*; D008076:Cholesterol, HDL / Q000378:metabolism*; D017931:DNA Primers; D004987:Ethers / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000096:biosynthesis / Q000235:genetics; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
D018955:CD36 Antigens; D008076:Cholesterol, HDL; D017931:DNA Primers; D004987:Ethers; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D000324:Adrenocorticotropic Hormone; D008071:Lipoprotein Lipase