title: Regulation of caveolin and caveolae by cholesterol in MDCK cells.
abstract: We have examined the expression of caveolin in MDCK cells under conditions that vary cellular cholesterol concentration. Caveolin mRNA levels dropped to one-sixth of control levels after treatment with simvastatin, an inhibitor of cholesterol synthesis, or beta-trimethyl cyclodextrin (CD), a cholesterol sequestering drug. Both simvastatin and CD treatment decreased total cellular cholesterol levels to about 50% of control values. The potent activator of the sterol regulatory element, 25-hydroxycholesterol, showed no direct regulation of caveolin mRNA levels. Caveolin protein concentration was also decreased to 50% of control values in cholesterol-depleted cells, giving rise to a severe attenuation of caveolin expression detected by indirect immunofluorescence labeling. Quantitative electron microscopy showed a total loss of morphologically recognizable invaginated caveolae after these cholesterol depletion treatments. When the number of invaginated caveolae per cell was expressed as a function of the cellular cholesterol content, a threshold phenomenon was observed, suggesting that caveolae only form when the steady state cellular cholesterol is above 50% of control values. These findings indicate that caveolins, and caveolae, may play an important part in cellular cholesterol homeostasis.
authors.affiliation: The Heart Research Institute, Camperdown NSW, Sydney, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Hailstones
authors.forename: L S
authors.initials: LS
authors.lastname: Sleer
authors.forename: R G
authors.initials: RG
authors.lastname: Parton
authors.forename: K K
authors.initials: KK
authors.lastname: Stanley
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051242:Caveolin 1; D022461:Caveolins; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure*; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000648:ultrastructure*; D008565:Membrane Proteins / Q000235:genetics*; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D012333:RNA, Messenger; D002784:Cholesterol