Research: Outside and in

6 January 2008

Rheumatoid arthritis is linked to the chemical modification of an ion channel by thioredoxin.

The small protein thioredoxin helps to maintain the oxidative balance inside the cell, but it has not been clear why it is also exported out of cells. Now, Professor David Beech (University of Leeds) and colleagues have revealed that this external thioredoxin is part of a cellular signalling system, the silencing of which may be a key step in the development of rheumatoid arthritis.

The researchers discovered that thioredoxin outside cells can activate a protein called TRPC5, causing it to allow positively charged ions into the cell.

The levels of thioredoxin in joints correlate with the severity of rheumatoid arthritis symptoms, leading the researchers to speculate that there is a connection between the two. They found that TRPC5 was expressed on the surface of cells in arthritic joints and, when TRPC5 channel activity was blocked in such cells, it responded by producing higher levels of several factors that promote the progression of arthritis.

References

Xu SZ et al. TRPC channel activation by extracellular thioredoxin. Nature 2008;451(7174):69-72.