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Effect-directed analysis reveals inhibition of zebrafish uptake transporter Oatp1d1 by caulerpenyne, a major secondary metabolite from the invasive marine alga Caulerpa taxifolia

Marić, Petra; Ahel, Marijan; Senta, Ivan; Terzić, Senka; Mikac, Iva; Žuljević, Ante; Smital, Tvrtko (2017) Effect-directed analysis reveals inhibition of zebrafish uptake transporter Oatp1d1 by caulerpenyne, a major secondary metabolite from the invasive marine alga Caulerpa taxifolia. Chemosphere, 174 . pp. 643-654. ISSN 0045-6535

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Abstract

Caulerpa taxifolia is a marine alga of tropical and subtropical distribution and a well-known invasive species in several temperate regions. Its invasiveness mainly stems from the production of secondary metabolites, some of which are toxic or repellent substances. In this study we investigated the possible inhibitory effects of C. taxifolia secondary metabolites on the activity of two zebrafish (Danio rerio) uptake transporters that transport organic anions (Oatp1d1) and cations (Oct1). Both transporters were transiently transfected and overexpressed in human embryonic kidney HEK293T cells. Transport activity assays using lucifer yellow (LY) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) as model substrates were applied for the determination of Oatp1d1 and Oct1 interactors. A two-step Effect-Directed Analysis (EDA) procedure was applied for the separation and identification of compounds. We identified caulerpenyne (CYN) as the major metabolite in C. taxifolia and reveal its potent inhibitory effect towards zebrafish Oatp1d1 as well as weak effect on zebrafish Oct1 transport. The observed effect was confirmed by testing CYN purified from C. taxifolia, resulting in an IC50 of 17.97 uM, and a weak CYN interaction was also determined for the zebrafish Oct1 transporter. Finally, using Michaelis-Menten kinetics experiments, we identified CYN as a non-competitive inhibitor of the zebrafish Oatp1d1. In conclusion, this study describes a novel mechanism of biological activity in C. taxifolia, shows that CYN was a potent non-competitive inhibitor of zebrafish Oatp1d1, and demonstrates that EDA can be reliably used for characterization of environmentally relevant complex biological samples.

Item Type: Article
Uncontrolled Keywords: Caulerpa taxifolia; Caulerpenyne; Oatp1d1; Oct1; Zebrafish; Effect-directed analysis (EDA)
Subjects: NATURAL SCIENCES > Biology > General Biology
NATURAL SCIENCES > Interdisciplinary Natural Sciences
NATURAL SCIENCES > Interdisciplinary Natural Sciences > Environmental Science
Divisions: Division for Marine and Enviromental Research
Projects:
Project titleProject leaderProject codeProject type
Identifikacija i funkcionalna karakterizacija (eko)toksikološki važnih polispecifičnih membranskih transportnih proteina u zebrici (Danio rerio)-TRANS-ZEBRATOXTvrtko SmitalIP-2013-11-4806HRZZ
Identification and characterization of cyanobacterial toxins based on their inter-action with basic cellular detoxification systems in zebrafish (Danio rerio) and zooplankton Daphnia magnaTvrtko SmitalSCOPES - IZ73ZO_152274/1).SNSF
Depositing User: Tvrtko Smital
Date Deposited: 23 Nov 2018 14:16
Last Modified: 23 Nov 2018 14:16
URI: http://fulir.irb.hr/id/eprint/4331
DOI: 10.1016/j.chemosphere.2017.02.007

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