Disruption of small molecule transporter systems by Transporter-Interfering Chemicals (TICs).
ABC transporter
SLC transporter
allosteric
chemosensitization
endogenous substrate competition
environmental
mixtures
signaling interference
small molecule transporter
transporter-interfering chemicals
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
30
08
2020
revised:
17
11
2020
accepted:
17
11
2020
pubmed:
23
11
2020
medline:
5
6
2021
entrez:
22
11
2020
Statut:
ppublish
Résumé
Small molecule transporters (SMTs) in the ABC and SLC families are important players in disposition of diverse endo- and xenobiotics. Interactions of environmental chemicals with these transporters were first postulated in the 1990s, and since validated in numerous in vitro and in vivo scenarios. Recent results on the co-crystal structure of ABCB1 with the flame-retardant BDE-100 demonstrate that a diverse range of man-made and natural toxic molecules, hereafter termed transporter-interfering chemicals (TICs), can directly bind to SMTs and interfere with their function. TIC-binding modes mimic those of substrates, inhibitors, modulators, inducers, and possibly stimulants through direct and allosteric mechanisms. Similarly, the effects could directly or indirectly agonize, antagonize or perhaps even prime the SMT system to alter transport function. Importantly, TICs are distinguished from drugs and pharmaceuticals that interact with transporters in that exposure is unintended and inherently variant. Here, we review the molecular mechanisms of environmental chemical interaction with SMTs, the methodological considerations for their evaluation, and the future directions for TIC discovery.
Identifiants
pubmed: 33222203
doi: 10.1002/1873-3468.14005
pmc: PMC8112642
mid: NIHMS1649725
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
ATP-Binding Cassette Transporters
0
Solute Carrier Proteins
0
Adenosine Triphosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
4158-4185Subventions
Organisme : NIEHS NIH HHS
ID : R01 ES027921
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030318
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES021985
Pays : United States
Informations de copyright
© 2020 Federation of European Biochemical Societies.
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