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

Scientific Reports
Jason GasparPedro Alvarez

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.

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Methods Mentioned

BETA
PCR
flow cytometry
Assay

Software Mentioned

Bio
Rad CFX manager

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