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Abstract:
A breakthrough in understanding the way atoms move across cell membranes in the human body could pave the way for the development of new treatments for inflammatory diseases such as rheumatoid arthritis.

‘Electronic switch’ opens doors in rheumatoid joints

Leeds, UK | Posted on January 3rd, 2008

Scientists at the University of Leeds have identified a previously unknown natural mechanism that opens ion channels - proteins at the cell surface that act as doorways into and out of cells - through the naturally occurring protein thioredoxin.

Ion channels allow movement of ions - electrically charged atoms - across the cell membrane to carry out various functions such as pain transmission, timing of the heart beat, and regulation of blood glucose. Often, they need to be stimulated to open and, until now, two main groups of activating mechanisms have been acknowledged: changes in cell voltage and binding of chemical factors.

In a paper published today (3 January) in Nature, Professor Beech and colleagues from the University's Faculty of Biological Sciences reveal that thioredoxin works in a different manner: it activates an ion channel by donating electrons to it, in a process Professor Beech likens to "an electronic on-switch".

"Thioredoxin is naturally present in cells and is secreted to help the body counter stressful chemical reactions that occur in inflammation, which can damage cells," he explains. "We already knew that inflammatory diseases cause the production of high levels of thioredoxin - in fact with rheumatoid arthritis, it's striking how much is present in affected joints. But we didn't know until now that thioredoxin can also activate ion channels, conferring additional protective potential and offering opportunities for mimicking the effect with drugs."

"It would seem that the body's own natural defences have provided us with new understanding that could be significant in the development of future treatments for arthritis and related diseases," he says.

The research has been funded by the Wellcome Trust, which has recently provided the group with further funding to expand its research into ion channels.

For further information contact:

Clare Elsley/Jo Kelly, campuspr, T: 0113 258 9880 or M: 07980 267756, Email: /

Guy Dixon, University of Leeds Press Office, T: 0113 343 8299, Email:

Notes to editors:

1. The research is published in this week's Nature in a paper entitled TRPC channel activation by extracellular thioredoxin. A copy of the paper is available to journalists on request.

2. Around 1 per cent of the UK population and approximately 2.1 million Americans suffer from rheumatoid arthritis - a painful inflammatory disorder, which leads to mild to moderate disability in most, with 10 per cent of sufferers having severe disability.

3. Professor Beech's team worked with rheumatologists from Leeds' St James's Hospital and the Carol Davila University, Bucharest, to show that the ion channel activated by thioredoxin is present and functional in arthritic joints.

4. David Beech is Professor of Molecular and Cellular Physiology and Director of the Institute of Membrane and Systems Biology at the University of Leeds' Faculty of Biological Sciences. His team's research interests are ion channels, including their roles in human disease and potential as novel therapeutic drug targets.

5. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research in the UK and internationally, spending around Ł500 million each year to support the brightest scientists and the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk

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About University of Leeds
The University of Leeds is acclaimed world-wide for the quality of its teaching and research. One of the largest universities in the UK, Leeds is also the most popular among students applying for undergraduate courses. An emphasis on innovative research and investment in high-quality facilities and first-rate infrastructure means that no fewer than 35 departments are rated internationally or nationally 'excellent'.

Its size and international reputation enables the University to offer one of the widest ranges of academic courses in the UK. During the current academic year over 32,241 students are attached to 700 different first-degree programmes and 474 postgraduate degree programmes. A further 26,544 men and women are enrolled on short courses with the University.

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