PMID- 34981808
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220318
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 135
IP  - 5
DP  - 2022 Mar 1
TI  - HDLs extract lipophilic drugs from cells.
LID - 10.1242/jcs.258644 [doi]
LID - jcs258644
AB  - 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.
CI  - (c) 2022. Published by The Company of Biologists Ltd.
FAU - Zheng, Adi
AU  - Zheng A
AUID- ORCID: 0000-0002-5632-1730
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Dubuis, Gilles
AU  - Dubuis G
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Georgieva, Maria
AU  - Georgieva M
AUID- ORCID: 0000-0002-4553-7894
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Mendes Ferreira, Carla Susana
AU  - Mendes Ferreira CS
AUID- ORCID: 0000-0002-2616-1940
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Serulla, Marc
AU  - Serulla M
AUID- ORCID: 0000-0002-4166-1556
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Del Carmen Conde Rubio, Maria
AU  - Del Carmen Conde Rubio M
AUID- ORCID: 0000-0002-0469-0227
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Trofimenko, Evgeniya
AU  - Trofimenko E
AUID- ORCID: 0000-0003-4910-5324
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
FAU - Mercier, Thomas
AU  - Mercier T
AUID- ORCID: 0000-0003-1921-4837
AD  - Laboratory of Clinical Pharmacology, Lausanne University Hospital (CHUV) and 
      University of Lausanne, 1011 Lausanne, Switzerland.
FAU - Decosterd, Laurent
AU  - Decosterd L
AUID- ORCID: 0000-0002-9840-1325
AD  - Laboratory of Clinical Pharmacology, Lausanne University Hospital (CHUV) and 
      University of Lausanne, 1011 Lausanne, Switzerland.
FAU - Widmann, Christian
AU  - Widmann C
AUID- ORCID: 0000-0002-6881-0363
AD  - Department of Biomedical Sciences, University of Lausanne, Bugnon 7, 1005 
      Lausanne, Switzerland.
LA  - eng
GR  - CRSII3_154420/Swiss National Science Foundation/Switzerland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220131
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Lipoproteins, HDL)
RN  - 0 (Pharmaceutical Preparations)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Endoplasmic Reticulum Stress
MH  - *Lipoproteins, HDL
MH  - *Pharmaceutical Preparations
MH  - Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics
MH  - Thapsigargin/pharmacology
PMC - PMC8919334
OTO - NOTNLM
OT  - Cell death
OT  - Doxorubicin
OT  - Drug efflux
OT  - Glibenclamide
OT  - HDL
OT  - High-density lipoprotein
OT  - Rhodamine 123
OT  - Staurosporine
OT  - Thapsigargin
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2022/01/05 06:00
MHDA- 2022/02/03 06:00
PMCR- 2022/01/31
CRDT- 2022/01/04 08:38
PHST- 2021/03/12 00:00 [received]
PHST- 2021/12/14 00:00 [accepted]
PHST- 2022/01/05 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2022/01/04 08:38 [entrez]
PHST- 2022/01/31 00:00 [pmc-release]
AID - 273878 [pii]
AID - JCS258644 [pii]
AID - 10.1242/jcs.258644 [doi]
PST - ppublish
SO  - J Cell Sci. 2022 Mar 1;135(5):jcs258644. doi: 10.1242/jcs.258644. Epub 2022 Jan 
      31.