| Regulatory role of β-arrestin-2 in cholesterol processing in cystic fibrosis epithelial cells. | |
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MedLine Citation:
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PMID: 22523395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cystic fibrosis (CF) cells exhibit an increase in the protein expression of β-arrestin-2 (βarr2) coincident with perinuclear accumulation of free cholesterol. Arrestins are proteins that both serve as broad signaling regulators and contribute to G-protein coupled receptor internalization after agonist stimulation. The hypothesis of this study is that βarr2 is an important component in the mechanisms leading to cholesterol accumulation characteristic of CF cells. To test this hypothesis, epithelial cells stably expressing GFP-tagged βarr2 (βarr2-GFP) and respective GFP-expressing control cells (cont-GFP) were analyzed by filipin staining. The βarr2-GFP cells show a late endosomal/lysosomal cholesterol accumulation that is identical to that seen in CF cells. This βarr2-mediated accumulation is sensitive to Rp-cAMPS treatment, and depleting βarr2 expression in CF-model cells by shRNA alleviates cholesterol accumulation compared with controls. Cftr/βarr2 double knockout mice also exhibit wild-type (WT) levels of cholesterol synthesis, and WT profiles of signaling protein expression have previously been shown to be altered in CF due to cholesterol-related pathways. These data indicate a significant regulatory role for βarr2 in the development of CF-like cholesterol accumulation and give further insight into cholesterol processing mechanisms. An impact of βarr2 expression on Niemann-Pick type C-1 (NPC1)-containing organelle movement is proposed as the mechanism of βarr2-mediated alterations on cholesterol processing. It is concluded that βarr2 expression contributes to altered cholesterol trafficking observed in CF cells. |
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Authors:
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Mary E Manson; Deborah A Corey; Ilya Bederman; James D Burgess; Thomas J Kelley |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-04-22 |
Journal Detail:
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Title: Journal of lipid research Volume: 53 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-11 Completed Date: 2013-02-26 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1268-76 Citation Subset: IM |
Affiliation:
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Departments of Chemistry, Case Western Reserve University, Cleveland, OH, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arrestins / deficiency, genetics, metabolism* Cells, Cultured Cholesterol / biosynthesis, genetics, metabolism* Cystic Fibrosis / genetics, metabolism* Epithelial Cells / metabolism*, pathology Humans Mice Mice, Inbred CFTR Mice, Knockout Phenotype |
| Grant Support | |
ID/Acronym/Agency:
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EB-009481/EB/NIBIB NIH HHS; HL-080319/HL/NHLBI NIH HHS; P30-DK-27651/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arrestins; 0/beta-arrestin; 57-88-5/Cholesterol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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