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...

Full description

Bibliographic Details
Main Authors: Jason Gaspar, Jacques Mathieu, Pedro Alvarez
Format: Article
Language:English
Published: Nature Publishing Group 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02387-8
id doaj-673ee66586584988aafa44748152d0ee
record_format Article
spelling doaj-673ee66586584988aafa44748152d0ee2020-12-08T02:04:27ZengNature Publishing GroupScientific 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
collection DOAJ
language English
format Article
sources DOAJ
author Jason Gaspar
Jacques Mathieu
Pedro Alvarez
spellingShingle Jason Gaspar
Jacques Mathieu
Pedro Alvarez
2-Hydroxypropyl-beta-cyclodextrin (HPβCD) reduces age-related lipofuscin accumulation through a cholesterol-associated pathway
Scientific Reports
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 Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-05-01
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.
url https://doi.org/10.1038/s41598-017-02387-8
work_keys_str_mv AT jasongaspar 2hydroxypropylbetacyclodextrinhpbcdreducesagerelatedlipofuscinaccumulationthroughacholesterolassociatedpathway
AT jacquesmathieu 2hydroxypropylbetacyclodextrinhpbcdreducesagerelatedlipofuscinaccumulationthroughacholesterolassociatedpathway
AT pedroalvarez 2hydroxypropylbetacyclodextrinhpbcdreducesagerelatedlipofuscinaccumulationthroughacholesterolassociatedpathway
_version_ 1724394169694158848

Similar Items