Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons
<p>Abstract</p> <p>Background</p> <p>Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-05-01
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| Series: | Molecular Neurodegeneration |
| Online Access: | http://www.molecularneurodegeneration.com/content/2/1/9 |
| _version_ | 1818058725563301888 |
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| author | Fujita Shinobu C Kobayashi Mariko Handa Tetsurou Morita Shin-ya Gong Jian-Sheng Yanagisawa Katsuhiko Michikawa Makoto |
| author_facet | Fujita Shinobu C Kobayashi Mariko Handa Tetsurou Morita Shin-ya Gong Jian-Sheng Yanagisawa Katsuhiko Michikawa Makoto |
| author_sort | Fujita Shinobu C |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified.</p> <p>Results</p> <p>Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3 or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with β-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3) or absence (apoE4) of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules.</p> <p>Conclusion</p> <p>These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.</p> |
| first_indexed | 2024-12-10T13:05:12Z |
| format | Article |
| id | doaj.art-73c10cc4e3a344ca9f390bdd3184c09f |
| institution | Directory Open Access Journal |
| issn | 1750-1326 |
| language | English |
| last_indexed | 2024-12-10T13:05:12Z |
| publishDate | 2007-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Neurodegeneration |
| spelling | doaj.art-73c10cc4e3a344ca9f390bdd3184c09f2022-12-22T01:47:53ZengBMCMolecular Neurodegeneration1750-13262007-05-0121910.1186/1750-1326-2-9Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neuronsFujita Shinobu CKobayashi MarikoHanda TetsurouMorita Shin-yaGong Jian-ShengYanagisawa KatsuhikoMichikawa Makoto<p>Abstract</p> <p>Background</p> <p>Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified.</p> <p>Results</p> <p>Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3 or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with β-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3) or absence (apoE4) of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules.</p> <p>Conclusion</p> <p>These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.</p>http://www.molecularneurodegeneration.com/content/2/1/9 |
| spellingShingle | Fujita Shinobu C Kobayashi Mariko Handa Tetsurou Morita Shin-ya Gong Jian-Sheng Yanagisawa Katsuhiko Michikawa Makoto Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons Molecular Neurodegeneration |
| title | Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons |
| title_full | Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons |
| title_fullStr | Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons |
| title_full_unstemmed | Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons |
| title_short | Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons |
| title_sort | novel action of apolipoprotein e apoe apoe isoform specifically inhibits lipid particle mediated cholesterol release from neurons |
| url | http://www.molecularneurodegeneration.com/content/2/1/9 |
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