Transporter-interfering chemicals inhibit P-glycoprotein of yellowfin tuna (Thunnus albacares)

Autor: Steven D. Rees, Sascha C.T. Nicklisch, Geoffrey Chang, Aaron P. McGrath, Amara Pouv, Amro Hamdoun
Rok vydání: 2021
Předmět:
0301 basic medicine
Physiology
Health
Toxicology and Mutagenesis
010501 environmental sciences
Toxicology
Medical and Health Sciences
01 natural sciences
Biochemistry
Yellowfin tuna
chemistry.chemical_compound
Water Pollutants
Cloning
Molecular
Phylogeny
Trophic level
Adenosine Triphosphatases
biology
Persistent organic pollutants
food and beverages
ABCB1
General Medicine
Biological Sciences
Bioaccumulation
Subfamily B
Liver
ABC transporter
fish physiology
Thunnus
Member 1
ATP Binding Cassette Transporter
Chemical
P-glycoprotein
DDT
03 medical and health sciences
Fish physiology
Animals
ATP Binding Cassette Transporter
Subfamily B
Member 1
Transporter-interfering chemicals
Life Below Water
0105 earth and related environmental sciences
Tuna
Molecular
Transporter
Cell Biology
biology.organism_classification
marine pollution
030104 developmental biology
chemistry
Gene Expression Regulation
Endrin
human activities
Environmental Sciences
Water Pollutants
Chemical
Cloning
Zdroj: Comparative biochemistry and physiology. Toxicologypharmacology : CBP. 248
ISSN: 1532-0456
Popis: Marine pollutants bioaccumulate at high trophic levels of marine food webs and are transferred to humans through consumption of apex species. Yellowfin tuna (Thunnus albacares) are marine predators, and one of largest commercial fisheries in the world. Previous studies have shown that yellowfin tuna can accumulate high levels of persistent organic pollutants, including Transporter Interfering Chemicals (TICs), which are chemicals shown to bind to mammalian xenobiotic transporters and interfere with their function. Here, we examined the extent to which these same compounds might interfere with the activity of the yellowfin tuna (Thunnus albacares) ortholog of this transporter. To accomplish this goal we identified, expressed, and functionally assayed tuna ABCB1. The results demonstrated a common mode of vertebrate ABCB1 interaction with TICs that predicts effects across these species, based on high conservation of specific interacting residues. Importantly several TICs showed potent inhibition of Ta-ABCB1, such as the organochlorine pesticides Endrin (EC50=1.2±0.2μM) and Mirex (EC50=2.3±0.9μM). However, unlike the effects observed on mouse ABCB1, low concentrations of the organochlorine pesticide TICs p,p'-DDT and its metabolite p,p'-DDD co-stimulated verapamil-induced Ta-ABCB1 ATPase activity possibly suggesting a low transport activity for these ligands in tuna. These results provide a mechanistic basis for understanding the potential vulnerability of tuna to these ubquitous pollutants.
Databáze: OpenAIRE
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