2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway
Abstract Oxidative stress causes significant increases in both cholesterol uptake and intracellular accumulation of the aging biomarker lipofuscin. Here we show that HPβCD addition mitigates these adverse effects in human fibroblasts by significantly reducing LDLr and SREBP1 gene expression. In the...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-02387-8 |
| _version_ | 1818683904117178368 |
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| author | Jason Gaspar Jacques Mathieu Pedro Alvarez |
| author_facet | Jason Gaspar Jacques Mathieu Pedro Alvarez |
| author_sort | Jason Gaspar |
| collection | DOAJ |
| description | Abstract Oxidative stress causes significant increases in both cholesterol uptake and intracellular accumulation of the aging biomarker lipofuscin. Here we show that HPβCD addition mitigates these adverse effects in human fibroblasts by significantly reducing LDLr and SREBP1 gene expression. In the absence of oxidative stress, HPβCD addition induces a paradoxical response, increasing cholesterol accumulation (but not lipofuscin) via upregulation of cholesterol biosynthesis. These two distinct, but opposite effects highlight a previously overlooked therapeutic consideration: the cholesterol content of the treated cell determines which cholesterol pathways, either beneficial or harmful, are responsive to HPβCD. |
| first_indexed | 2024-12-17T10:42:08Z |
| format | Article |
| id | doaj.art-673ee66586584988aafa44748152d0ee |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-17T10:42:08Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-673ee66586584988aafa44748152d0ee2022-12-21T21:52:14ZengNature PortfolioScientific Reports2045-23222017-05-01711710.1038/s41598-017-02387-82-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathwayJason Gaspar0Jacques Mathieu1Pedro Alvarez2Rice University, Dept of Civil and Environmental EngineeringRice University, Dept of Civil and Environmental EngineeringRice University, Dept of Civil and Environmental EngineeringAbstract Oxidative stress causes significant increases in both cholesterol uptake and intracellular accumulation of the aging biomarker lipofuscin. Here we show that HPβCD addition mitigates these adverse effects in human fibroblasts by significantly reducing LDLr and SREBP1 gene expression. In the absence of oxidative stress, HPβCD addition induces a paradoxical response, increasing cholesterol accumulation (but not lipofuscin) via upregulation of cholesterol biosynthesis. These two distinct, but opposite effects highlight a previously overlooked therapeutic consideration: the cholesterol content of the treated cell determines which cholesterol pathways, either beneficial or harmful, are responsive to HPβCD.https://doi.org/10.1038/s41598-017-02387-8 |
| spellingShingle | Jason Gaspar Jacques Mathieu Pedro Alvarez 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway Scientific Reports |
| title | 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway |
| title_full | 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway |
| title_fullStr | 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway |
| title_full_unstemmed | 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway |
| title_short | 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway |
| title_sort | 2 hydroxypropyl beta cyclodextrin hpβcd reduces age related lipofuscin accumulation through a cholesterol associated pathway |
| url | https://doi.org/10.1038/s41598-017-02387-8 |
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