2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway

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...

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Autores principales: Jason Gaspar, Jacques Mathieu, Pedro Alvarez
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
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R
Science
Q
Acceso en línea:https://doaj.org/article/673ee66586584988aafa44748152d0ee
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spelling oai:doaj.org-article:673ee66586584988aafa44748152d0ee2021-12-02T11:40:58Z2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway10.1038/s41598-017-02387-82045-2322https://doaj.org/article/673ee66586584988aafa44748152d0ee2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02387-8https://doaj.org/toc/2045-2322Abstract 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.Jason GasparJacques MathieuPedro AlvarezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jason Gaspar
Jacques Mathieu
Pedro Alvarez
2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway
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.
format article
author Jason Gaspar
Jacques Mathieu
Pedro Alvarez
author_facet Jason Gaspar
Jacques Mathieu
Pedro Alvarez
author_sort Jason Gaspar
title 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_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_sort 2-hydroxypropyl-beta-cyclodextrin (hpβcd) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/673ee66586584988aafa44748152d0ee
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AT jacquesmathieu 2hydroxypropylbetacyclodextrinhpbcdreducesagerelatedlipofuscinaccumulationthroughacholesterolassociatedpathway
AT pedroalvarez 2hydroxypropylbetacyclodextrinhpbcdreducesagerelatedlipofuscinaccumulationthroughacholesterolassociatedpathway
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