Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers.
In confluent fibroblast monolayers, an increase in the selective uptake of free cholesterol (FC) from plasma low density lipoprotein (LDL) was accompanied by an increase in FC efflux. The rate of FC efflux was proportional to the FC content of the cell surface caveolae and to mRNA levels of caveolin, an FC-binding protein of caveolae. Inhibitors of LDL-FC internalization reduced the increase in caveolin mRNA levels and FC efflux. Oxysterols reduced caveolin mRNA levels, as well as transport of FC to the cell surface and FC efflux. DNA antisense to caveolin reduced caveolin mRNA and inhibited FC efflux. These data suggest that regulation of FC efflux can contribute to cellular FC homeostasis when LDL levels are modified over the physiological range, and they link this regulation to caveolin.
Fielding
C J
CJ
Cardiovascular Research Institute, Department of Physiology, University of California Medical Center, San Francisco 94143, USA.
Bist
A
A
Fielding
P E
PE
D001692:Biological Transport; D051242:Caveolin 1; D022461:Caveolins; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D002784:Cholesterol