A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts
Identifieur interne : 000B77 ( Pmc/Corpus ); précédent : 000B76; suivant : 000B78A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts
Auteurs : Ulrike Schueler ; Christine Kaneski ; Alan Remaley ; Stephen Demosky ; Nancy Dwyer ; Joan Blanchette-Mackie ; John Hanover ; Roscoe BradySource :
- JIMD Reports [ 2192-8304 ] ; 2015.
Abstract
Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal–lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal–lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.
Url:
DOI: 10.1007/8904_2015_507
PubMed: 26683465
PubMed Central: 5059196
Links to Exploration step
PMC:5059196Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts</title><author><name sortKey="Schueler, Ulrike" sort="Schueler, Ulrike" uniqKey="Schueler U" first="Ulrike" last="Schueler">Ulrike Schueler</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Kaneski, Christine" sort="Kaneski, Christine" uniqKey="Kaneski C" first="Christine" last="Kaneski">Christine Kaneski</name><affiliation><nlm:aff id="Aff14">NINDS National Institutes of Health, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Remaley, Alan" sort="Remaley, Alan" uniqKey="Remaley A" first="Alan" last="Remaley">Alan Remaley</name><affiliation><nlm:aff id="Aff15">NHLBI Lipoprotein Metabolism Section, National Institutes of Health, Bethesda, MD USA</nlm:aff></affiliation></author><author><name sortKey="Demosky, Stephen" sort="Demosky, Stephen" uniqKey="Demosky S" first="Stephen" last="Demosky">Stephen Demosky</name><affiliation><nlm:aff id="Aff15">NHLBI Lipoprotein Metabolism Section, National Institutes of Health, Bethesda, MD USA</nlm:aff></affiliation></author><author><name sortKey="Dwyer, Nancy" sort="Dwyer, Nancy" uniqKey="Dwyer N" first="Nancy" last="Dwyer">Nancy Dwyer</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Blanchette Mackie, Joan" sort="Blanchette Mackie, Joan" uniqKey="Blanchette Mackie J" first="Joan" last="Blanchette-Mackie">Joan Blanchette-Mackie</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Hanover, John" sort="Hanover, John" uniqKey="Hanover J" first="John" last="Hanover">John Hanover</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Brady, Roscoe" sort="Brady, Roscoe" uniqKey="Brady R" first="Roscoe" last="Brady">Roscoe Brady</name><affiliation><nlm:aff id="Aff14">NINDS National Institutes of Health, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26683465</idno><idno type="pmc">5059196</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059196</idno><idno type="RBID">PMC:5059196</idno><idno type="doi">10.1007/8904_2015_507</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000B77</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000B77</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts</title><author><name sortKey="Schueler, Ulrike" sort="Schueler, Ulrike" uniqKey="Schueler U" first="Ulrike" last="Schueler">Ulrike Schueler</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Kaneski, Christine" sort="Kaneski, Christine" uniqKey="Kaneski C" first="Christine" last="Kaneski">Christine Kaneski</name><affiliation><nlm:aff id="Aff14">NINDS National Institutes of Health, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Remaley, Alan" sort="Remaley, Alan" uniqKey="Remaley A" first="Alan" last="Remaley">Alan Remaley</name><affiliation><nlm:aff id="Aff15">NHLBI Lipoprotein Metabolism Section, National Institutes of Health, Bethesda, MD USA</nlm:aff></affiliation></author><author><name sortKey="Demosky, Stephen" sort="Demosky, Stephen" uniqKey="Demosky S" first="Stephen" last="Demosky">Stephen Demosky</name><affiliation><nlm:aff id="Aff15">NHLBI Lipoprotein Metabolism Section, National Institutes of Health, Bethesda, MD USA</nlm:aff></affiliation></author><author><name sortKey="Dwyer, Nancy" sort="Dwyer, Nancy" uniqKey="Dwyer N" first="Nancy" last="Dwyer">Nancy Dwyer</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Blanchette Mackie, Joan" sort="Blanchette Mackie, Joan" uniqKey="Blanchette Mackie J" first="Joan" last="Blanchette-Mackie">Joan Blanchette-Mackie</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Hanover, John" sort="Hanover, John" uniqKey="Hanover J" first="John" last="Hanover">John Hanover</name><affiliation><nlm:aff id="Aff13">NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author><author><name sortKey="Brady, Roscoe" sort="Brady, Roscoe" uniqKey="Brady R" first="Roscoe" last="Brady">Roscoe Brady</name><affiliation><nlm:aff id="Aff14">NINDS National Institutes of Health, Bethesda, MD 20892-0851 USA</nlm:aff></affiliation></author></analytic><series><title level="j">JIMD Reports</title><idno type="ISSN">2192-8304</idno><idno type="eISSN">2192-8312</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal–lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal–lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">JIMD Rep</journal-id><journal-id journal-id-type="iso-abbrev">JIMD Rep</journal-id><journal-title-group><journal-title>JIMD Reports</journal-title></journal-title-group><issn pub-type="ppub">2192-8304</issn><issn pub-type="epub">2192-8312</issn><publisher><publisher-name>Springer Berlin Heidelberg</publisher-name><publisher-loc>Berlin, Heidelberg</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">26683465</article-id><article-id pub-id-type="pmc">5059196</article-id><article-id pub-id-type="publisher-id">507</article-id><article-id pub-id-type="doi">10.1007/8904_2015_507</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Schueler</surname><given-names>Ulrike</given-names></name><address><email>hoffmanu@niddk.nih.gov</email></address><xref ref-type="aff" rid="Aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Kaneski</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="Aff14">14</xref></contrib><contrib contrib-type="author"><name><surname>Remaley</surname><given-names>Alan</given-names></name><xref ref-type="aff" rid="Aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Demosky</surname><given-names>Stephen</given-names></name><xref ref-type="aff" rid="Aff15">15</xref></contrib><contrib contrib-type="author"><name><surname>Dwyer</surname><given-names>Nancy</given-names></name><xref ref-type="aff" rid="Aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Blanchette-Mackie</surname><given-names>Joan</given-names></name><xref ref-type="aff" rid="Aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Hanover</surname><given-names>John</given-names></name><xref ref-type="aff" rid="Aff13">13</xref></contrib><contrib contrib-type="author"><name><surname>Brady</surname><given-names>Roscoe</given-names></name><xref ref-type="aff" rid="Aff14">14</xref></contrib><aff id="Aff13"><label>13</label>NIDDK, LCBB, National Institutes of Health, Building 8, Room 420, 8 Center Drive, Bethesda, MD 20892-0851 USA</aff><aff id="Aff14"><label>14</label>NINDS National Institutes of Health, Bethesda, MD 20892-0851 USA</aff><aff id="Aff15"><label>15</label>NHLBI Lipoprotein Metabolism Section, National Institutes of Health, Bethesda, MD USA</aff></contrib-group><contrib-group content-type="collaborators"><contrib contrib-type="Series editor"><name><surname>Baumgartner</surname><given-names>Matthias R.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="Series editor"><name><surname>Patterson</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="Series editor"><name><surname>Rahman</surname><given-names>Shamima</given-names></name><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="Series editor"><name><surname>Peters</surname><given-names>Verena</given-names></name><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="Editor-in-chief"><name><surname>Morava</surname><given-names>Eva</given-names></name><xref ref-type="aff" rid="Aff5">5</xref></contrib><contrib contrib-type="Series editor"><name><surname>Zschocke</surname><given-names>Johannes</given-names></name><xref ref-type="aff" rid="Aff6">6</xref></contrib><aff id="Aff1"><label>1</label>Division of Metabolism, University Children’s Hospital, Zurich, Switzerland</aff><aff id="Aff2"><label>2</label>Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, Minnesota USA</aff><aff id="Aff3"><label>3</label>Health, Genetics & Genomic Med Clinical and Molecular Genetics Unit, Univ Coll London Inst of Child, London, United Kingdom</aff><aff id="Aff4"><label>4</label>Managing Editor JIMD Univ Children´s Hospital Heidelberg, Univ Children´s Hospital Heidelberg, Heidelberg, Germany</aff><aff id="Aff5"><label>5</label>Hayward Genetics Ctr,SL#31, Tulane Univ Medical Health Ctr, New Orleans, Louisiana USA</aff><aff id="Aff6"><label>6</label>Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria</aff></contrib-group><author-notes><fn fn-type="com"><p>Communicated by: Gregory M. Pastores, MD</p></fn></author-notes><pub-date pub-type="epub"><day>19</day><month>12</month><year>2015</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>29</volume><fpage>69</fpage><lpage>75</lpage><history><date date-type="received"><day>20</day><month>09</month><year>2015</year></date><date date-type="rev-recd"><day>20</day><month>09</month><year>2015</year></date><date date-type="accepted"><day>29</day><month>09</month><year>2015</year></date></history><permissions><copyright-statement>© SSIEM and Springer-Verlag Berlin Heidelberg 2015</copyright-statement></permissions><abstract id="Abs1"><p>Fabry disease is an X-linked sphingolipid storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (AGA, EC 3.2.1.22) resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal–lysosomal cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal–lysosomal trafficking. We found that LDL receptor expression is not downregulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. 5A-Palmitoyl oleoyl-phosphatidylcholine (5AP) is a phospholipid complex containing a short synthetic peptide that mimics apolipoprotein A1, the main protein component of high-density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. We used 5AP and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using immunostaining techniques, we found that 5AP is highly effective for depleting cholesterol and Gb3 in these cells. 5AP restores the ApoA-1-mediated cholesterol efflux leading to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.</p></abstract><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© SSIEM and Springer-Verlag Berlin Heidelberg 2016</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/LymphedemaV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B77 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 000B77 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= LymphedemaV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:5059196
|texte= A Short Synthetic Peptide Mimetic of Apolipoprotein A1 Mediates Cholesterol and Globotriaosylceramide Efflux from Fabry Fibroblasts
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:26683465" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a LymphedemaV1
| This area was generated with Dilib version V0.6.31. |  |