Enzymatic oxidation of cholesterol: Properties and functional effects of cholestenone in cell membranes

30Citations
Citations of this article
27Readers
Mendeley users who have this article in their library.

Abstract

Bacterial cholesterol oxidase is commonly used as an experimental tool to reduce cellular cholesterol content. That the treatment also generates the poorly degradable metabolite 4-cholesten-3-one (cholestenone) has received less attention. Here, we investigated the membrane partitioning of cholestenone using simulations and cell biological experiments and assessed the functional effects of cholestenone in human cells. Atomistic simulations predicted that cholestenone reduces membrane order, undergoes faster flip-flop and desorbs more readily from membranes than cholesterol. In primary human fibroblasts, cholestenone was released from membranes to physiological extracellular acceptors more avidly than cholesterol, but without acceptors it remained in cells over a day. To address the functional effects of cholestenone, we studied fibroblast migration during wound healing. When cells were either cholesterol oxidase treated or part of cellular cholesterol was exchanged for cholestenone with cyclodextrin, cell migration during 22 h was markedly inhibited. Instead, when a similar fraction of cholesterol was removed using cyclodextrin, cells replenished their cholesterol content in 3 h and migrated similarly to control cells. Thus, cholesterol oxidation produces long-term functional effects in cells and these are in part due to the generated membrane active cholestenone. © 2014 Neuvonen et al.

Cite

CITATION STYLE

APA

Neuvonen, M., Manna, M., Mokkila, S., Javanainen, M., Rog, T., Liu, Z., … Ikonen, E. (2014). Enzymatic oxidation of cholesterol: Properties and functional effects of cholestenone in cell membranes. PLoS ONE, 9(8). https://doi.org/10.1371/journal.pone.0103743

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free