HDLs extract lipophilic drugs from cells.

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License: CC BY 4.0
Serval ID
serval:BIB_74F4A1CDF17E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HDLs extract lipophilic drugs from cells.
Journal
Journal of cell science
Author(s)
Zheng A., Dubuis G., Georgieva M., Mendes Ferreira C.S., Serulla M., Del Carmen Conde Rubio M., Trofimenko E., Mercier T., Decosterd L., Widmann C.
ISSN
1477-9137 (Electronic)
ISSN-L
0021-9533
Publication state
Published
Issued date
01/03/2022
Peer-reviewed
Oui
Volume
135
Number
5
Pages
jcs258644
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
High-density lipoproteins (HDLs) prevent cell death induced by a variety of cytotoxic drugs. The underlying mechanisms are however still poorly understood. Here, we present evidence that HDLs efficiently protect cells against thapsigargin (TG), a sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA) inhibitor, by extracting the drug from cells. Drug efflux could also be triggered to some extent by low-density lipoproteins and serum. HDLs did not reverse the non-lethal mild ER stress response induced by low TG concentrations or by SERCA knockdown, but HDLs inhibited the toxic SERCA-independent effects mediated by high TG concentrations. HDLs could extract other lipophilic compounds, but not hydrophilic substances. This work shows that HDLs utilize their capacity of loading themselves with lipophilic compounds, akin to their ability to extract cellular cholesterol, to reduce the cell content of hydrophobic drugs. This can be beneficial if lipophilic xenobiotics are toxic but may be detrimental to the therapeutic benefit of lipophilic drugs such as glibenclamide.
Keywords
Calcium/metabolism, Endoplasmic Reticulum/metabolism, Endoplasmic Reticulum Stress, Lipoproteins, HDL, Pharmaceutical Preparations, Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics, Thapsigargin/pharmacology, Cell death, Doxorubicin, Drug efflux, Glibenclamide, HDL, High-density lipoprotein, Rhodamine 123, Staurosporine, Thapsigargin
Pubmed
Web of science
Open Access
Yes
Create date
11/01/2022 14:46
Last modification date
19/07/2023 7:12
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