Press release September 3, 2013
Fish Embryos Possess a Mechanism for Protection against Chemicals
UFZ researchers discover function of protein as transporter of toxic chemicals in the zebrafish embryo
Leipzig/Dübendorf (Switzerland). Researchers at the Helmholtz Centre for Envi-ronmental Research (UFZ), together with colleagues from the Swiss Eawag aquatic research institute, have discovered a protein which transports chemicals out of the embryo of the zebrafish and in this way protects the embryo against toxic substances. However, certain environmental chemicals render this protective mechanism ineffective, so that the fish embryos become more sensitive to toxic substances. The study, published in the scientific journal "BMC Biology", could prove to be of great importance for the future assessment of chemicals.
Fish possess a number of different mechanisms for protection against harmful substances in an aquatic environment. These include, for example, molecular transport systems, such as the so called ABC (ATP binding cassette) transporters, which prevent the penetration of toxic substances into cells. ABC transporters have been well investigated for mammals. For fish and their embryos, however, little is known about such transporters. Ecotoxicologists Dr. Till Luckenbach (UFZ) and Dr. Stephan Fischer (Eawag) together with other colleagues have now found that the transport protein Abcb4 actively extrudes chemicals from the embryo of the zebrafish (Danio rerio). "A fish embryo already has effective protective capabilities", says Luckenbach. "The importance of such transport systems is generally underestimated in toxicological and ecotoxicological research – but they play a very important role."
When a substance is bound to zebrafish Abcb4 , this triggers cleavage of the energy transfer substance adenosine triphosphate (ATP). The energy which this sets free is utilised to expel this substance from the cell. Abcb4 can repel a multitude of different chemical compounds, as a result of which the embryo is resistant to a multitude of toxic substances. In humans the protein ABCB1 serves this function. Thus, it came as a surprise that it is Abcb4 that in zebrafish acts as “multidrug” or “multixenobiotic” trans-porter. The homologous ABCB4 of humans, by contrast, is incapable of transporting toxic chemical compounds. Instead, human ABCB4 has a specific function in liver where it channels certain fatty acids into the bile ducts in order to protect the liver cells against aggressive biliary acids.
In experiments with zebrafish embryos in which the expression of Abcb4 protein was suppressed, Luckenbach and his team found that the embryos were much more sensi-tive to toxic chemicals and that these substances were enriched to a greater extent in the embryo tissue. "Based on this data we concluded that the zebrafish Abcb4 protects the embryo against the toxic impact of chemicals by keeping them out", says Luckenbach.
In follow-on investigations the researchers measured the activity of the transport system, enabling the identification of the chemicals which Abcb4 transports. However, certain substances block the transport mechanism. This inhibition renders its function ineffective, and other harmful substances can penetrate into the organism. "Compounds which inhibit the transporter throw open the doorway for other toxic substances ", says Stephan Fischer." These are also referred to as chemosensitizers, as they make the organism more sensitive to harmful chemicals. This indirect toxic effect plays an important role, above all in mixtures of substances such as frequently found in our environment."
At the UFZ a wide range of environmentally relevant chemicals are currently being investigated for their impact on the Abcb4 transporter system – separately and in mix-tures.
Luckenbach: "Many effects of substance mixtures may be explained on the basis of the zebrafish Abcb4 protein activity. Zebrafish embryos are used for the assessment of chemicals and for
investigations of environmental impact, so we hope that in future our study will contribute to an awareness of the need to incorporate Abcb4 transport processes in toxicological testing
Abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish (Danio rerio) embryos
Stephan Fischer, Nils Klüver, Kathleen Burkhardt-Medicke, Mirko Pietsch, Anne-Marie Schmidt, Peggy Wellner, Kristin Schirmer and Till Luckenbach
BMC Biology 2013, 11:69 doi:10.1186/1741-7007-11-69
Partial funding was provided for this work by the Deutsche Forschungsgemeinschaft (DFG), the Ministry of Environment, Agriculture and Geology of Saxony and the the German Federal Environmental Foundation (DBU).
Dr. Till Luckenbach
Helmholtz Centre for Environmental Research(UFZ)
Phone +49 341 235 1514
Dr. Till Luckenbach
Dr. Stephan Fischer
Eawag / Wasserforschungs-Institut des ETH-Bereichs (Schweiz)
Phone +41 58 765 55 67
Dr. Stephan Fischer
Tilo Arnhold / Susanne Hufe (UFZ press office)
Phone +49 341 235 1630
At the Helmholtz Centre for Environmental Research (UFZ) scientists are researching the causes and consequences of far-reaching changes to the environment. They are concerned with water resources, biological diversity, the consequences of climate change and adaptability, environmental and biotechnologies, bioenergy, the behaviour of chemicals in the environment, their effect on health, modelling and social science issues. Their guiding theme: Our research contributes to the sustainable use of natural resources and helps to secure this basis for life over the long term under the effects of global change. The UFZ employs more than 1,100 people in Leipzig, Halle and Magdeburg. It is financed by the federal government and the federal states of Saxony and Saxony-Anhalt.
The Helmholtz Association contributes towards solving major and pressing social, scientific and economic issues with scientific excellence in six research areas: Energy, Earth and Environment, Health, Key Technologies, Structure of Matter, Aeronautics, Aerospace and Transport. The Helmholtz Association is Germany’s largest scientific organisation with nearly 34,000 employees in 18 research centres and an annual budget of approximately 3.8 billion euros. Its work stands in the tradition of the naturalist Hermann von Helmholtz (1821-1894).