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What causes cell defences to crumble? - Researchers identify proteins in mussels that act as a barrier to chemicals

09.10.2008
Cells have mechanisms that allow them to deal with harmful substances and to survive.

One such protective mechanism consists of transport proteins in the cell membrane that act as molecular 'pumps', preventing toxic compounds from accumulating in the cell. This defence mechanism against toxic chemicals is called multi-xenobiotic resistance (MXR). Substances that inhibit the MXR mechanism are called chemosensitizers.

The two recently discovered proteins are both ABC transporters. This class of membrane proteins takes its name from a shared structural element: the ATP-binding cassette (ABC). ABC transporters are one of the largest known families of proteins that occur in organisms ranging from bacteria to mammals.

Similar proteins are involved in the blood-brain barrier in humans, where they prevent harmful substances from entering the sensitive nerve tissue. In mussels and other aquatic organisms this barrier does not divide different parts of the same organism, but forms a barrier towards the outside - an 'environment-tissue barrier'.

"The proteins are in the cell membrane and ensure that substances that do not belong in the cell are transported out again - like a bilge pump that pumps water out of a ship," explains Dr Till Luckenbach of the UFZ.

Possible effects of environmental chemicals on the MXR system were first described nearly 20 years ago. But it is only in recent years that scientists have begun investigating such effects in more detail. "We want to understand the system to find out how chemicals interact with these transporters," says Luckenbach, who began researching mussels at Stanford University's Hopkins Marine Station in California and is continuing his research using fish and mammalian cells in Leipzig at the Helmholtz Centre for Environmental Research.

"So far, comparatively little is known about environment-related substances that trigger this chemical sensitization by blocking the MXR system.

However, the known substances belong to very different chemical groups. This could be an indication that interactions between environmental substances and the system are widespread."

Until now, the chemicals authorisation procedure has been looking at associated risks, such as toxicity and mutagenic or carcinogenic effects. The sensitization effect of certain substances with regard to other chemicals - referred to as the chemosensitization effect by scientists – does not play a role in the current legislation. However, Till Luckenbach and his colleagues are convinced that these substances have a major impact on the environment and that it is important to find out more about these processes.

Publications:
Luckenbach, T., Epel, D., (2008):
ABCB and ABCC type transporters confer multixenobiotic resistance and form an environment-tissue barrier in bivalve gills. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 294(6):R1919-29.
doi:10.1152/ajpregu.00563.2007
http://ajpregu.physiology.org/cgi/content/abstract/294/6/R1919
This publication was supported in part by the Deutsche Forschungsgemeinschaft (DFG), the National Sea Grant College Program of the US Department of Commerce (National Oceanic and Atmospheric Administration) and the California State Resources Agency.
Epel D., Luckenbach T., Stevenson C.N., MacManus-Spencer L.A., Hamdoun A., Smital T., (2008):
Efflux transporters: newly appreciated roles in protection against pollutants. Environmental Science & Technology, 42(11):3914-3920.
http://pubs.acs.org/subscribe/journals/esthag/42/i11/html/
060108feature_epel.html
Support for this work came from National Science Foundation (NSF), the German Research Council and others.
More Informations:
Dr. Till Luckenbach
Helmholtz Centre for Environmental Research (UFZ)
Telephone: +49-341-235-1514
und
Prof. David Epel
Hopkins Marine Station, Stanford University Tel. +1-(831) 655-6226
or from
Tilo Arnhold (UFZ press office)
Telephone: +49 (0)341 235 1269
Email: presse@ufz.de
Links:
Department of Cell Toxicology:
http://www.ufz.de/index.php?en=2821
Hopkins Marine Station of Stanford University http://www-marine.stanford.edu/ http://www.stanford.edu/~depel/ National Sea Grant College Program:

http://www.seagrant.noaa.gov/

At the Helmholtz Centre for Environmental Research (UFZ) scientists research the causes and consequences of far-reaching environmental changes. They study water resources, biological diversity, the consequences of climate change and adaptation possibilities, environmental and biotechnologies, bio energy, the behaviour of chemicals in the environment and their effect on health, as well as modelling and social science issues. Their guiding research principle is supporting the sustainable use of natural resources and helping to secure these basic requirements of life over the long term under the influence of global change. The UFZ employs 900 people at its sites in Leipzig, Halle and Magdeburg. It is funded by the German government and by the states of Saxony and Saxony-Anhalt.

The Helmholtz Association helps solve major, pressing challenges facing society, science and the economy with top scientific achievements in six research areas: Energy, Earth and Environment, Health, Key Technologies, Structure of Matter, Transport and Space. With 25,700 employees in 15 research centres and an annual budget of around EUR 2.3 billion, the Helmholtz Association is Germanys largest scientific organisation. Its work follows in the tradition of the great natural scientist Hermann von Helmholtz (1821-1894).

Tilo Arnhold | UFZ Leipzig-Halle
Further information:
http://www.ufz.de/index.php?en=17251
http://www.ufz.de/index.php?en=15560
http://www-marine.stanford.edu/epel.htm

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