Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

Citrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreitol (DTT) are normally added to the reaction buffer when determining PAD activity in vitro. We investigated the ability of reduced glutathione (GSH), the most abundant intracellular small-molecule thiol in vivo, to activate PADs. Activity of recombinant human (rh) PAD2 and PAD4, PADs contained in synovial fluid (SF... Mehr ...