HDLs extract lipophilic drugs from cells.
Cell death
Doxorubicin
Drug efflux
Glibenclamide
HDL
High-density lipoprotein
Rhodamine 123
Staurosporine
Thapsigargin
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
received:
12
03
2021
accepted:
14
12
2021
pubmed:
5
1
2022
medline:
3
2
2022
entrez:
4
1
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34981808
pii: 273878
doi: 10.1242/jcs.258644
pmc: PMC8919334
pii:
doi:
Substances chimiques
Lipoproteins, HDL
0
Pharmaceutical Preparations
0
Thapsigargin
67526-95-8
Sarcoplasmic Reticulum Calcium-Transporting ATPases
EC 3.6.3.8
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : CRSII3_154420
Pays : Switzerland
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
Références
Hum Mol Genet. 1995 Aug;4(8):1403-9
pubmed: 7581381
Methods Enzymol. 2008;442:395-419
pubmed: 18662581
Clin Liver Dis. 2017 Feb;21(1):1-20
pubmed: 27842765
Eur J Biochem. 1999 Oct 1;265(1):273-80
pubmed: 10491183
FEBS Lett. 1998 Nov 13;439(1-2):9-12
pubmed: 9849867
Front Pharmacol. 2018 Oct 15;9:1154
pubmed: 30374303
Sci Rep. 2017 Mar 03;7:42717
pubmed: 28256516
Cardiovasc Res. 2014 Aug 1;103(3):384-94
pubmed: 24903496
J Clin Invest. 1955 Sep;34(9):1345-53
pubmed: 13252080
J Lipids. 2018 Aug 6;2018:3965054
pubmed: 30174957
Acta Pharm Sin B. 2018 Jan;8(1):51-63
pubmed: 29872622
Oncotarget. 2019 Dec 17;10(66):7058-7070
pubmed: 31903165
Curr Opin Lipidol. 2016 Jun;27(3):264-73
pubmed: 27031272
J Drug Target. 2013 May;21(4):367-74
pubmed: 23600747
Nat Rev Cardiol. 2011 Apr;8(4):222-32
pubmed: 21304474
J Drug Target. 2010 Jan;18(1):53-8
pubmed: 19637935
Cell Calcium. 1999 Jun;25(6):419-28
pubmed: 10579053
J Biol Chem. 2006 Mar 17;281(11):6970-6
pubmed: 16410239
Mol Cell Endocrinol. 2013 Dec 5;381(1-2):291-301
pubmed: 23994023
Cell Signal. 2019 Oct;62:109347
pubmed: 31229616
Adv Med Biol. 2012;53:199-216
pubmed: 25392741
Methods Enzymol. 2011;491:57-71
pubmed: 21329794
Trends Endocrinol Metab. 2011 Jan;22(1):9-15
pubmed: 21067941
Diabetes. 2012 May;61(5):1100-11
pubmed: 22399686
Int J Mol Sci. 2019 Dec 15;20(24):
pubmed: 31847457
J Biol Chem. 2001 Sep 14;276(37):34480-5
pubmed: 11432865
Diabetes. 2016 Oct;65(10):3039-52
pubmed: 27489309
Front Pharmacol. 2019 Mar 05;10:208
pubmed: 30890942
Nucleic Acids Res. 2014 Jul;42(12):8049-61
pubmed: 24875475
J Clin Invest. 2004 Feb;113(4):569-81
pubmed: 14966566
Atherosclerosis. 1990 Jul;83(1):35-45
pubmed: 2117929
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Curr Drug Deliv. 2004 Jan;1(1):27-42
pubmed: 16305368
Mol Cancer Ther. 2018 May;17(5):943-951
pubmed: 29467273
Biochem Soc Trans. 2011 Jun;39(3):789-97
pubmed: 21599650
Biochim Biophys Acta. 2006 Jul;1761(7):655-66
pubmed: 16798073
Front Cardiovasc Med. 2020 Mar 31;7:39
pubmed: 32296714
Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1732-8
pubmed: 12920050
N Engl J Med. 2007 Sep 27;357(13):1301-10
pubmed: 17898099
J Lipid Res. 2013 Mar;54(3):671-676
pubmed: 23288948
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
Biochem J. 2001 Jun 15;356(Pt 3):805-12
pubmed: 11389688
Cell Death Discov. 2021 Jun 19;7(1):164
pubmed: 34226511
J Biol Chem. 2002 Feb 8;277(6):3801-4
pubmed: 11733542
Elife. 2019 Mar 13;8:
pubmed: 30864945
Nat Rev Endocrinol. 2012 Jan 24;8(4):237-45
pubmed: 22271188
Diabetes. 2015 Sep;64(9):3328-33
pubmed: 25972569
Circ Res. 2019 May 10;124(10):1505-1518
pubmed: 31071007