title: Increased expression of caveolin-1 in heterozygous Niemann-Pick type II human fibroblasts.
abstract: Human Niemann-Pick type II fibroblasts, which encompass the panethnic type C (NPC) and Nova Scotia Acadian type D (NPD) variants, exhibit altered expression of caveolin-1 protein when examined by immunoblotting using an anti-caveolin-1 monoclonal antibody. Unexpectedly, caveolin-1 in heterozygous fibroblasts was significantly elevated as much as 10-fold compared to caveolin-1 in normal and homozygous affected fibroblasts. Homozygous NPC fibroblasts expressed caveolin-1 levels similar to those in normal fibroblasts, while the expression of caveolin-1 in homozygous NPD fibroblasts was slightly elevated. Northern analysis indicates that normal fibroblasts and NPC heterozygous fibroblasts have similar amounts of caveolin-1 mRNA, while NPC homozygous fibroblasts have significantly less caveolin-1 mRNA. In contrast, heterozygous and homozygous NPD fibroblasts exhibit increased levels of caveolin-1 mRNA. These novel findings suggest that caveolin-1 containing subcellular structures are involved in the pathophysiology of Niemann-Pick type II disease. Furthermore, altered caveolin-1 protein expression may serve as a useful marker for the diagnosis of carriers of NPC or NPD.
authors.affiliation: Angel Charity for Children Wings for Genetic Research, Steele Memorial Children's Research Center, The University of Arizona, College of Medicine, Tucson 85724, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Garver
authors.forename: S C
authors.initials: SC
authors.lastname: Hsu
authors.forename: R P
authors.initials: RP
authors.lastname: Erickson
authors.forename: W L
authors.initials: WL
authors.lastname: Greer
authors.forename: D M
authors.initials: DM
authors.lastname: Byers
authors.forename: R A
authors.initials: RA
authors.lastname: Heidenreich
mesh_terms: D051242:Caveolin 1; D022461:Caveolins; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009542:Niemann-Pick Diseases / Q000235:genetics / Q000378:metabolism*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins