Researchers at the Helmholtz Centre for Environmental 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" transporter. 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 sensitive 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 mixtures. 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 directives." Nicole Silbermann
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, 11:69doi: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)
Dr. Stephan Fischer
Eawag / Aquatic Research Institute of the Swiss Federal Institute of Technology
Telephone: +41 (0)58 765 55 67
Tilo Arnhold / Susanne Hufe (UFZ Press Office)
Telephone: 0341-235-1635, -1630
At Helmholtz Centre for Environmental Research (UFZ), scientists research the causes and ramifications of far-reaching changes in the environment. They focus on water resources, biological diversity, the consequences of climate change and means of adaptation, environmental and bio-technologies, bio-energy, how chemicals behave in the environment, their repercussions on health, modelling and questions of social sciences. Their leitmotif: our research serves the sustainable use of natural resources and, under the influence of climate change, helps safeguard these foundations of life for posterity. UFZ employs a staff of 1,100 employees at its sites in Leipzig, Halle and Magdeburg. Its funding comes from the Federal Government and the states of Saxony and Saxony Anhalt.
The Helmholtz Association contributes to solving major and urgent questions within society, sciences and industry through the provision of academic excellence in six fields of research: energy, the earth and environment, health, key technologies, structure of matter and aviation, aerospace and transport. Employing a staff of 35,000 in 18 research centres and equipped with an annual budget in the region of 3.8 billion euro, the Helmholtz Association is Germany's largest scientific organisation. Its work stands in the tradition of the outstanding natural scientist Hermann von Helmholtz (1821-1894).
Nicole Silbermann/Tilo Arnhold | Source: UFZ News
Further information: www.ufz.de/index.php?en=31974
Further Reports about: ABC Transporters > chemical compounds > chemical engineering > Embryo > Environmental Research > environmental risk > fatty acid > Fish > harmful substances > Helmholtz > mechanism > natural resource > Protection > social science > toxic chemical > toxic substance > transport systems > UFZ > water resource > zebrafish embryo
More articles from Life Sciences:
Toxigenic C. difficile resides harmlessly in infants, poses risk to adults
04.12.2013 | American Society for Microbiology
Bacteria like the taste of syngas
04.12.2013 | Evonik Industries AG
Quantum entanglement, a perplexing phenomenon of quantum mechanics that Albert Einstein once referred to as “spooky action at a distance,” could be even spookier than Einstein perceived.
Physicists at the University of Washington and Stony Brook University in New York believe the phenomenon might be intrinsically linked with wormholes, hypothetical features of space-time that in popular science fiction can provide a much-faster-than-light shortcut from one part of the universe to another.
But here’s the catch: One couldn’t actually ...
A star is formed when a large cloud of gas and dust condenses and eventually becomes so dense that it collapses into a ball of gas, where the pressure heats the matter, creating a glowing gas ball – a star is born.
New research from the Niels Bohr Institute, among others, shows that a young, newly formed star in the Milky Way had such an explosive growth, that it was initially about 100 times brighter than it is now. The results are published in the scientific journal, Astrophysical Journal Letters.
The young ...
EPFL scientists have shown how to achieve a dramatic increase in the capacity of optical fibers; Their simple, innovative solution reduces the amount of space required between the pulses of light that transport data
Optical fibers carry data in the form of pulses of light over distances of thousands of miles at amazing speeds. They are one of the glories of modern telecommunications technology.
However, their capacity is limited, because the pulses of light need to be lined up one after the other in ...
NASA's Hurricane and Severe Storms Sentinel airborne mission known as HS3 wrapped up for the 2013 Atlantic Ocean hurricane season at the end of September, and had several highlights. HS3 will return to NASA’s Wallops Flight Facility in Wallops Island, Va., for the 2014 Atlantic hurricane season.
During the 2013 mission, two unmanned Global Hawks flew from Wallops for the first time. The mission highlights included studying the Saharan Air Layer, following the genesis of a tropical storm, finding a unique hybrid core or center circulation in a redeveloped storm, obtaining measurements on the strongest side of ...
Nanosponges that soak up a dangerous pore-forming toxin produced by MRSA (methicillin-resistant Staphylococcus aureus) could serve as a safe and effective vaccine against this toxin.
This "nanosponge vaccine" enabled the immune systems of mice to block the adverse effects of the alpha-haemolysin toxin from MRSA—both within the bloodstream and on the skin. Nanoengineers from the University of California, San Diego described the safety and efficacy of this nanosponge vaccine in the December 1 issue of ...
04.12.2013 | Health and Medicine
04.12.2013 | Materials Sciences
04.12.2013 | Ecology, The Environment and Conservation
04.12.2013 | Event News
12.11.2013 | Event News
29.10.2013 | Event News