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Content archived on 2024-05-29

Interaction of toxic organotin compounds towards human metallothionein-3

Objective

Metallothioneins (MTs) are low-molecular-weight metalloproteins (MPs) with high cysteine (Cys) content. They are involved in a wide range of biochemical processes. In human MT-1 and MT-2 isoforms are found in all organs, whereas MT-3 is expressed mainly in the brain. Human exposure to organotin compounds (OTs) stems from their use as polyvinyl chloride heat stabilizers and as marine biocides. Certain OTs have already been detected in blood, liver or urine samples from individuals. Acute exposures can result in either neurotoxicity or immunotoxicity depending on the specific compound involved. Recently, attention has been focused on the biological chemistry of OTs. It has been shown, that Cys is one of the primary biological ligands for OTs. Regarding to its high Cys content, it is likely that main target of OTs in brain cells is MT-3.

The objective of this project is to study the interaction of human MT-3 towards four neuro- and immunotoxic OTs detected in drinking water and in biological samples from human b ody. The conditions of the over-expression, purification and the conversion to an air-stable derivative of recombinant MT-3 will be optimised first. Incorporation of OTs into MTs, composition of the resulting new MP(s) will be studied by electrospray ionisation mass spectrometry (ESI MS), inductively coupled plasma atom emission spectrometry (ICP AES), circular dicroism (CD) and ultraviolet-visible (UV-Vis) spectrophotometry. The incorporation of OTs into Zn-MT-3 under physiological conditions will also be studied. Finally, the inductive effect of OTs on the over-expression of MT-3 will be monitored as a control.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-11
See other projects for this call

Funding Scheme

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ERG - Marie Curie actions-European Re-integration Grants

Coordinator

UNIVERSITY OF SZEGED
EU contribution
No data
Total cost

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