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Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model

BACKGROUND: The plasma membrane scavenger receptor, SR-BI, mediates the 'selective uptake' process by which cholesteryl esters (CE) from exogenously supplied HDL are taken up by target cells. Recent work suggests that dimer and higher order oligomeric forms of the SR-BI protein are importa...

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Autores principales: Reaven, Eve, Nomoto, Ann, Cortez, Yuan, Azhar, Salman
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764879/
https://www.ncbi.nlm.nih.gov/pubmed/17173681
http://dx.doi.org/10.1186/1743-7075-3-43
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author Reaven, Eve
Nomoto, Ann
Cortez, Yuan
Azhar, Salman
author_facet Reaven, Eve
Nomoto, Ann
Cortez, Yuan
Azhar, Salman
author_sort Reaven, Eve
collection PubMed
description BACKGROUND: The plasma membrane scavenger receptor, SR-BI, mediates the 'selective uptake' process by which cholesteryl esters (CE) from exogenously supplied HDL are taken up by target cells. Recent work suggests that dimer and higher order oligomeric forms of the SR-BI protein are important to this process. SR-BI has been shown to be particularly associated with microvilli and microvillar channels found at the cell surface of steroidogenic cells, and a study with the hormone stimulated adrenal gland has shown impressive changes in the size and complexity of the microvillar compartment as the mass of CE uptake (and accompanying steroidogenesis) fluctuates. In the present study, we examine a cell line in which we overexpress the SR-BI protein to determine if morphological, biochemical and functional events associated with SR-BI in a controlled cell system are similar to those observed in the intact mammalian adrenal which is responsive to systemic factors. METHODS: Y1-BS1 mouse adrenocortical cells were transiently transfected using rat SR-BI-pcDNA6-V5-His, rat SR-BI-pcDNA6-cMyc-His or control pcDNA6-V5-His vector construct using a CaPO(4 )precipitation technique. Twenty four hours after transfection, cells were treated with, or without, Bt(2)cAMP, and SR-BI expression, CE uptake, and steroidogenesis was measured. SR-BI dimerization and cell surface architectural changes were assessed using immunoelectron microscopic techniques. RESULTS: Overexpression of the scavenger receptor protein, SR-BI, in Y1-BS1 cells results in major alterations in cell surface architecture designed to increase uptake of HDL supplied-CEs. Changes include [1] the formation of crater-like erosions of the surface with multiple double membraned channel structures lining the craters, and [2] dimerized formations of SR-BI lining the newly formed craters and associated double membraned channels. CONCLUSION: These data show that overexpression of the scavenger receptor protein, SR-BI (accompanied by suitable hormone treatment and lipoproteins) in susceptible mammalian cells – is associated with increased cholesterol uptake and SR-BI dimerization within a much enlarged and architecturally complex microvillar compartment. These changes duplicate the structural, biochemical and functional changes related to the uptake of HDL CEs normally signaled by the action of ACTH on intact adrenal tissue.
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spelling pubmed-17648792007-01-10 Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model Reaven, Eve Nomoto, Ann Cortez, Yuan Azhar, Salman Nutr Metab (Lond) Research BACKGROUND: The plasma membrane scavenger receptor, SR-BI, mediates the 'selective uptake' process by which cholesteryl esters (CE) from exogenously supplied HDL are taken up by target cells. Recent work suggests that dimer and higher order oligomeric forms of the SR-BI protein are important to this process. SR-BI has been shown to be particularly associated with microvilli and microvillar channels found at the cell surface of steroidogenic cells, and a study with the hormone stimulated adrenal gland has shown impressive changes in the size and complexity of the microvillar compartment as the mass of CE uptake (and accompanying steroidogenesis) fluctuates. In the present study, we examine a cell line in which we overexpress the SR-BI protein to determine if morphological, biochemical and functional events associated with SR-BI in a controlled cell system are similar to those observed in the intact mammalian adrenal which is responsive to systemic factors. METHODS: Y1-BS1 mouse adrenocortical cells were transiently transfected using rat SR-BI-pcDNA6-V5-His, rat SR-BI-pcDNA6-cMyc-His or control pcDNA6-V5-His vector construct using a CaPO(4 )precipitation technique. Twenty four hours after transfection, cells were treated with, or without, Bt(2)cAMP, and SR-BI expression, CE uptake, and steroidogenesis was measured. SR-BI dimerization and cell surface architectural changes were assessed using immunoelectron microscopic techniques. RESULTS: Overexpression of the scavenger receptor protein, SR-BI, in Y1-BS1 cells results in major alterations in cell surface architecture designed to increase uptake of HDL supplied-CEs. Changes include [1] the formation of crater-like erosions of the surface with multiple double membraned channel structures lining the craters, and [2] dimerized formations of SR-BI lining the newly formed craters and associated double membraned channels. CONCLUSION: These data show that overexpression of the scavenger receptor protein, SR-BI (accompanied by suitable hormone treatment and lipoproteins) in susceptible mammalian cells – is associated with increased cholesterol uptake and SR-BI dimerization within a much enlarged and architecturally complex microvillar compartment. These changes duplicate the structural, biochemical and functional changes related to the uptake of HDL CEs normally signaled by the action of ACTH on intact adrenal tissue. BioMed Central 2006-12-15 /pmc/articles/PMC1764879/ /pubmed/17173681 http://dx.doi.org/10.1186/1743-7075-3-43 Text en Copyright © 2006 Reaven et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Reaven, Eve
Nomoto, Ann
Cortez, Yuan
Azhar, Salman
Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title_full Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title_fullStr Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title_full_unstemmed Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title_short Consequences of over-expression of rat Scavenger Receptor, SR-BI, in an adrenal cell model
title_sort consequences of over-expression of rat scavenger receptor, sr-bi, in an adrenal cell model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1764879/
https://www.ncbi.nlm.nih.gov/pubmed/17173681
http://dx.doi.org/10.1186/1743-7075-3-43
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