| Intracellular Cholesterol Binding Proteins Enhance HDL-mediated Cholesterol Uptake in Cultured Primary Mouse Hepatocytes. | |
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MedLine Citation:
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PMID: 22241858 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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A major gap in our knowledge of rapid hepatic high density lipoprotein (HDL) cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport (RCT) pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein-2 (SCP2) and liver fatty acid binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, HDL-mediated free cholesterol uptake were examined using gene targeted mouse models, cultured primary hepatocytes, and NBD-cholesterol. While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also: (i) enhanced the rapid molecular phase of free sterol uptake detectable in <1min, initial rate, and maximal uptake of HDL-free cholesterol; and (ii) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than HDL2, subfraction. The increased HDL-free cholesterol uptake was not due to increased expression or distribution of the HDL receptor (scavenger receptor B1, SRB1), proteins regulating SRB1 (PDZK-1, MAP17), or other intracellular cholesterol trafficking proteins (StARDs, NPCs, ORPs). However, expression of L-FABP-the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated 2-fold in SCP-2/SCP-x null hepatocytes. Double immunogold EM detected L-FABP sufficiently close to SRB1 for direct interaction-similar to SCP-2. These data suggested a role for L-FABP in HDL-cholesterol uptake-a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together, these results suggest that L-FABP, particularly in the absence of SCP-2, plays a significant role in HDL-mediated cholesterol uptake in cultured primary hepatocytes. |
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Authors:
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Stephen M Storey; Avery L McIntosh; Huan Huang; Kerstin K Landrock; Gregory G Martin; Danilo Landrock; H Ross Payne; Barbara P Atshaves; Ann B Kier; Friedhelm Schroeder |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: - ISSN: 1522-1547 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Texas A&M University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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