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Pregled bibliografske jedinice broj: 939765

The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos


Dragojević, Jelena; Mihaljević, Ivan; Popović, Marta; Žaja, Roko; Smital, Tvrtko
The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos // Aquatic toxicology (2018) (znanstveni, poslan)


CROSBI ID: 939765 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos

Autori
Dragojević, Jelena ; Mihaljević, Ivan ; Popović, Marta ; Žaja, Roko ; Smital, Tvrtko

Vrsta, podvrsta
Radovi u časopisima, znanstveni

Izvornik
Aquatic toxicology (2018)

Status rada
Poslan

Ključne riječi
zebrafish, steroid hormones, Oatp1d1 knockouts, physiological endpoints, Oatp1d1 inhibition, environmental contaminants

Sažetak
Hydrophobic cholesterol-derived steroids are traditionally thought to enter the target cells by passive difusion. However, in recent studies role of specific transport proteins from the ABC and the Solute Carrier (SLC) superfamily of proteins has been demonstrated in mediating transport of steroids into and out of the cells. Accordingly, specific human and/or mammalian organic anion transporting polypeptides (OATPs) were shown to transport steroid and thyroid hormones or their conjugates. Yet, the functional properties of related transporters in fish remain poorly investigated, and the same is true for zebrafish as an important model in biomedical and environmental research. Based on these premises we have previously identified, characterized in vitro, and classified a new member of the fish Oatp1 group – Oatp1d1. We also showed that steroid hormones are potent interactors with zebrafish Oatp1d1, and identified several environmental contaminants as potent Oatp1d1 inhibitors. In this study we address the effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos in vivo, using functional genomics studies with zebrafish Oatp1d1 knockouts developed using the CRISPR/Cas9 gene editing. Genotypization of the knockout embryos was performed using the High Resolution Melting (HRM) analysis, and DNA sequencing used for final verification of embryos that were used in exposure experiments. Overall health status and a series of physiological endpoints of wildtype and Oatp1d1 knockout embryos was evaluated upon 1-120 hpf exposures to selected steroid hormones (E2, P4, DHEAS, cortisol) with and without addition of various concentrations of environemntal Oatp1d1 inhibitors (diclofenac, PFOS, PFOA). Anylyses of physiological endpoints in the exposed WT and knockout embryos (muscle contraction in 24 hpf embryos, hatching success in 48 hpf, 60 hpf and 72 hpf, heart rate in 48 hpf embryos, and swimming activity in 120 hpf embryos) revealed significant differences, strongly implying the role of zebrafish Oatp1d1 in uptake of steroid hormones. The obtained data strongly suggest that the role of OATP/Oatp transporters in steroid catabolism could be evolutionary conserved from fish to mammals. Finally, modulation of transport function of Oatp1d1 by environmental contaminants could interfere with the Oatp1d1 mediated transport of steroids.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekti:
HRZZ 4806

Ustanove:
Institut "Ruđer Bošković", Zagreb

Profili:

Avatar Url Jelena Dragojević (autor)

Avatar Url Roko Žaja (autor)

Avatar Url Tvrtko Smital (autor)

Avatar Url Marta Popović (autor)


Citiraj ovu publikaciju

Dragojević, Jelena; Mihaljević, Ivan; Popović, Marta; Žaja, Roko; Smital, Tvrtko
The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos // Aquatic toxicology (2018) (znanstveni, poslan)
Dragojević, J., Mihaljević, I., Popović, M., Žaja, R. & Smital, T. (2018) The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos. Poslan u Aquatic toxicology. [Preprint].
@unknown{unknown, year = {2018}, keywords = {zebrafish, steroid hormones, Oatp1d1 knockouts, physiological endpoints, Oatp1d1 inhibition, environmental contaminants}, journal = {Aquatic toxicology}, title = {The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos}, keyword = {zebrafish, steroid hormones, Oatp1d1 knockouts, physiological endpoints, Oatp1d1 inhibition, environmental contaminants} }
@unknown{unknown, year = {2018}, keywords = {zebrafish, steroid hormones, Oatp1d1 knockouts, physiological endpoints, Oatp1d1 inhibition, environmental contaminants}, journal = {Aquatic toxicology}, title = {The effects of environmental pollutants on the Oatp1d1 mediated uptake of steroids in zebrafish embryos}, keyword = {zebrafish, steroid hormones, Oatp1d1 knockouts, physiological endpoints, Oatp1d1 inhibition, environmental contaminants} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE





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