What causes cell defenses to crumble?

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Photo: Till Luckenbach/UFZ

Source: UFZ

Pacific Grove (CA)/Leipzig. Researchers have for the first time identified complete gene sequences and function of two proteins in mussels that play a key defensive role against environmental toxicants. These proteins form part of an active, physiological barrier in mussel gills that protects them against environmental toxicants, researchers from the Helmholtz Centre for Environmental Research (UFZ) in Germany and Stanford University in California report in the American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. Mussels like the California mussel (Mytilus californianus) can pump over 20 litres of water through their gills every hour. The active barrier protects the organism against harmful substances in the water. The presence of such proteins in mussel gills has been previously indicated, but it is only now that they can be accurately identified. The function of these proteins can be inhibited by chemicals introduced into the environment by humans, e.g. galaxolide, a perfume used in cleaning products. This means that such substances open the way for other chemicals to enter cells. Even chemicals that are not regarded as toxic by conventional standards can enhance toxicity of other compounds. Little is known about the global environmental and human impacts of these 'chemosensitizers'. 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 (Germany) 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.

Source: Helmholtz Association of German Research Centres