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

Kristin Tietje¹  Georgina Rivera-Ingraham²  Charlotte Petters³  Doris Abele²  Ralf Dringen³ 

[1] Carl von Ossietzky University Oldenburg, Carl von Ossietzky Str. 9-11, Oldenburg D-26111, Germany; E-Mail:;Alfred-Wegener-Institut Helmholtz-Zentrum für Polar- und Meeresforschung, Am Handelshafen 12, Bremerhaven D-27570, Germany; E-Mails:;Centre for Biomolecular Interactions Bremen, University of Bremen, P.O. Box 33 04 40, Bremen D-28334, Germany; E-Mails:

关键词: 2-photon laser scanning microscopy;    natural product;    fluorescence;    live imaging;    ABC transporter;   

DOI  :  10.3390/md11103951

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.