Mar. Drugs 2013, 11(10), 3951-3969; doi:10.3390/md11103951
Article

Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters

1 Carl von Ossietzky University Oldenburg, Carl von Ossietzky Str. 9-11, Oldenburg D-26111, Germany 2 Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Am Handelshafen 12, Bremerhaven D-27570, Germany 3 Centre for Biomolecular Interactions Bremen, University of Bremen, P.O. Box 33 04 40, Bremen D-28334, Germany
* Author to whom correspondence should be addressed.
Received: 10 July 2013; in revised form: 26 August 2013 / Accepted: 27 September 2013 / Published: 16 October 2013
(This article belongs to the Special Issue Cytogenetic and Molecular Effects of Marine Compounds)
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Abstract: The marine plathyhelminth Macrostomum lignano was recently isolated from Adriatic shore sediments where it experiences a wide variety of environmental challenges, ranging from hypoxia and reoxygenation, feeding on toxic algae, to exposure to anthropogenic contaminants. As multidrug resistance transporters constitute the first line of defense against toxins and toxicants we have studied the presence of such transporters in M. lignano in living animals by applying optical methods and pharmacological inhibitors that had been developed for mammalian cells. Application of the MDR1 inhibitor Verapamil or of the MRP1 inhibitors MK571 or Probenecid increased the intracellular fluorescence of the reporter dyes Fura-2 am, Calcein am, Fluo-3 am in the worms, but did not affect their staining with the dyes Rhodamine B, CMFDA or Ageladine A. The marine sponge alkaloid Ageladine A remained intracellularly trapped for several days in the worms, suggesting that it does not serve as substrate of multidrug resistance exporters. In addition, Ageladine A did not affect multidrug resistance-associated protein (MRP)-mediated dye export from M. lignano or the MRP1-mediated glutathione (GSH) export from cultured rat brain astrocytes. The data obtained demonstrate that life-imaging is a useful tool to address physiological drug export from intact marine transparent flatworms by using multiphoton scanning microscopy.
Keywords: 2-photon laser scanning microscopy; natural product; fluorescence; live imaging; ABC transporter

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MDPI and ACS Style

Tietje, K.; Rivera-Ingraham, G.; Petters, C.; Abele, D.; Dringen, R.; Bickmeyer, U. Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters. Mar. Drugs 2013, 11, 3951-3969.

AMA Style

Tietje K, Rivera-Ingraham G, Petters C, Abele D, Dringen R, Bickmeyer U. Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters. Marine Drugs. 2013; 11(10):3951-3969.

Chicago/Turabian Style

Tietje, Kristin; Rivera-Ingraham, Georgina; Petters, Charlotte; Abele, Doris; Dringen, Ralf; Bickmeyer, Ulf. 2013. "Reporter Dyes Demonstrate Functional Expression of Multidrug Resistance Proteins in the Marine Flatworm Macrostomum lignano: The Sponge-Derived Dye Ageladine A Is Not a Substrate of These Transporters." Mar. Drugs 11, no. 10: 3951-3969.

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