title: Essentially all excess fibroblast cholesterol moves from plasma membranes to intracellular compartments.
abstract: It has been shown that modestly increasing plasma membrane cholesterol beyond its physiological set point greatly increases the endoplasmic reticulum and mitochondrial pools, thereby eliciting manifold feedback responses that return cell cholesterol to its resting state. The question arises whether this homeostatic mechanism reflects the targeting of cell surface cholesterol to specific intracellular sites or its general equilibration among the organelles. We now show that human fibroblast cholesterol can be increased as much as two-fold from 2-hydroxypropyl-β-cyclodextrin without changing the size of the cell surface pool. Rather, essentially all of the added cholesterol disperses rapidly among cytoplasmic membranes, increasing their overall cholesterol content by as much as five-fold. We conclude that the level of plasma membrane cholesterol is normally at capacity and that even small increments above this physiological set point redistribute essentially entirely to intracellular membranes, perhaps down their chemical activity gradients.
authors.affiliation: Department of Pathology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lange
authors.affiliation: Department of Pathology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Jin
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Steck
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D052816:Foreskin / Q000166:cytology / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D061251:Primary Cell Culture; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002784:Cholesterol