Cyclic AMP stimulates the synthesis and function of the low-density lipoprotein receptor in human vascular smooth-muscle cells and fibroblasts.
Identifieur interne : 002E22 ( Main/Exploration ); précédent : 002E21; suivant : 002E23Cyclic AMP stimulates the synthesis and function of the low-density lipoprotein receptor in human vascular smooth-muscle cells and fibroblasts.
Auteurs : B. Middleton [Royaume-Uni] ; A. MiddletonSource :
- The Biochemical journal [ 0264-6021 ] ; 1992.
Descripteurs français
- KwdFr :
- AMP cyclique (métabolisme), AMP cyclique (pharmacologie), AMP cyclique (physiologie), Activation chimique, Cellules cultivées, Cholestérol (biosynthèse), Cholestérol (déficit), Cholestérol (métabolisme), Cholestérol ester (métabolisme), Fibroblastes (métabolisme), Fibroblastes (physiologie), Fibroblastes (ultrastructure), Humains, Muscles lisses vasculaires (métabolisme), Muscles lisses vasculaires (physiologie), Muscles lisses vasculaires (ultrastructure), Oxydoréduction, Récepteurs aux lipoprotéines LDL (), Récepteurs aux lipoprotéines LDL (biosynthèse), Récepteurs aux lipoprotéines LDL (physiologie), Régulation positive (physiologie), Stérols (métabolisme).
- MESH :
- biosynthèse : Cholestérol, Récepteurs aux lipoprotéines LDL.
- déficit : Cholestérol.
- métabolisme : AMP cyclique, Cholestérol, Cholestérol ester, Fibroblastes, Muscles lisses vasculaires, Stérols.
- pharmacologie : AMP cyclique.
- physiologie : AMP cyclique, Fibroblastes, Muscles lisses vasculaires, Récepteurs aux lipoprotéines LDL, Régulation positive.
- Activation chimique, Cellules cultivées, Fibroblastes, Humains, Muscles lisses vasculaires, Oxydoréduction, Récepteurs aux lipoprotéines LDL.
English descriptors
- KwdEn :
- Cells, Cultured, Cholesterol (biosynthesis), Cholesterol (deficiency), Cholesterol (metabolism), Cholesterol Esters (metabolism), Cyclic AMP (metabolism), Cyclic AMP (pharmacology), Cyclic AMP (physiology), Fibroblasts (metabolism), Fibroblasts (physiology), Fibroblasts (ultrastructure), Humans, Muscle, Smooth, Vascular (metabolism), Muscle, Smooth, Vascular (physiology), Muscle, Smooth, Vascular (ultrastructure), Oxidation-Reduction, Receptors, LDL (biosynthesis), Receptors, LDL (drug effects), Receptors, LDL (physiology), Sterols (metabolism), Stimulation, Chemical, Up-Regulation (physiology).
- MESH :
- chemical , biosynthesis : Cholesterol, Receptors, LDL.
- chemical , deficiency : Cholesterol.
- chemical , drug effects : Receptors, LDL.
- chemical , metabolism : Cholesterol, Cholesterol Esters, Cyclic AMP, Sterols.
- chemical , pharmacology : Cyclic AMP.
- chemical , physiology : Cyclic AMP, Receptors, LDL.
- metabolism : Fibroblasts, Muscle, Smooth, Vascular.
- physiology : Fibroblasts, Muscle, Smooth, Vascular, Up-Regulation.
- ultrastructure : Fibroblasts, Muscle, Smooth, Vascular.
- Cells, Cultured, Humans, Oxidation-Reduction, Stimulation, Chemical.
Abstract
1. Cyclic AMP-elevating agents stimulate low-density lipoprotein (LDL) receptor activity in human vascular smooth-muscle cells by increasing the rate of receptor protein synthesis. The stimulation is not secondary to the decrease in the regulatory pool of free cholesterol, since it is unaffected, or even enhanced, by inhibition of cholesterol synthesis and esterification, or inhibition of the conversion of cholesterol into its repressor metabolites. The cyclic AMP-mediated up-regulation of the receptor is maintained at low concentrations of inhibitory sterols, but is eventually over-ridden at high concentrations of these sterols. 2. Cyclic AMP-elevating agents also stimulate the hydrolysis of lysosomal cholesterol esters, thus increasing the cellular cholesterol pool and repressing the expression of the LDL receptor. This cholesterol-mediated repressive effect of cyclic AMP can be prevented by chloroquine, which inhibits lysosomal actions, or by ketoconazole, which inhibits conversion of free cholesterol into its repressor metabolite. Thus the cyclic AMP stimulation of the LDL receptor can be masked by the rapid mobilization of free cholesterol from existing cholesterol esters within cultured cells. 3. We have observed that elevated cyclic AMP concentrations will up-regulate the LDL receptor in cholesterol-depleted human vascular smooth-muscle cells, skin fibroblasts and foetal-lung fibroblasts. We propose that our results are evidence for a cyclic AMP-stimulated, sterol-independent, control of LDL-receptor synthesis which is of widespread occurrence in human cells.
DOI: 10.1042/bj2820853
PubMed: 1313231
Affiliations:
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Le document en format XML
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Middleton</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre, U.K.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biochemistry, University of Nottingham Medical School, Queen's Medical Centre</wicri:regionArea><wicri:noRegion>Queen's Medical Centre</wicri:noRegion></affiliation></author><author><name sortKey="Middleton, A" sort="Middleton, A" uniqKey="Middleton A" first="A" last="Middleton">A. 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Cyclic AMP-elevating agents stimulate low-density lipoprotein (LDL) receptor activity in human vascular smooth-muscle cells by increasing the rate of receptor protein synthesis. The stimulation is not secondary to the decrease in the regulatory pool of free cholesterol, since it is unaffected, or even enhanced, by inhibition of cholesterol synthesis and esterification, or inhibition of the conversion of cholesterol into its repressor metabolites. The cyclic AMP-mediated up-regulation of the receptor is maintained at low concentrations of inhibitory sterols, but is eventually over-ridden at high concentrations of these sterols. 2. Cyclic AMP-elevating agents also stimulate the hydrolysis of lysosomal cholesterol esters, thus increasing the cellular cholesterol pool and repressing the expression of the LDL receptor. This cholesterol-mediated repressive effect of cyclic AMP can be prevented by chloroquine, which inhibits lysosomal actions, or by ketoconazole, which inhibits conversion of free cholesterol into its repressor metabolite. Thus the cyclic AMP stimulation of the LDL receptor can be masked by the rapid mobilization of free cholesterol from existing cholesterol esters within cultured cells. 3. We have observed that elevated cyclic AMP concentrations will up-regulate the LDL receptor in cholesterol-depleted human vascular smooth-muscle cells, skin fibroblasts and foetal-lung fibroblasts. We propose that our results are evidence for a cyclic AMP-stimulated, sterol-independent, control of LDL-receptor synthesis which is of widespread occurrence in human cells.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><noCountry><name sortKey="Middleton, A" sort="Middleton, A" uniqKey="Middleton A" first="A" last="Middleton">A. Middleton</name></noCountry><country name="Royaume-Uni"><noRegion><name sortKey="Middleton, B" sort="Middleton, B" uniqKey="Middleton B" first="B" last="Middleton">B. Middleton</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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