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Sci Rep. 2017 May 19;7(1):2197. doi: 10.1038/s41598-017-02387-8.

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

Author information

1
Rice University, Dept of Civil and Environmental Engineering, MS-6398, 6100 Main Street, Houston, TX, 77005, USA.
2
Rice University, Dept of Civil and Environmental Engineering, MS-6398, 6100 Main Street, Houston, TX, 77005, USA. mathieu@rice.edu.
3
Rice University, Dept of Civil and Environmental Engineering, MS-6398, 6100 Main Street, Houston, TX, 77005, USA. alvarez@rice.edu.

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.

PMID:
28526856
PMCID:
PMC5438378
DOI:
10.1038/s41598-017-02387-8
[Indexed for MEDLINE]
Free PMC Article

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