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Reactive oxygen species inhibit catalytic activity of peptidylarginine deiminase.


ABSTRACT: Protein citrullination catalysed by peptidylarginine deiminase (PAD) may play an important pathogenic role in several chronic inflammatory diseases and malignancies. PAD2, PAD4, and citrullinated proteins are found in the synovium of rheumatoid arthritis patients. PAD activity is dependent on calcium and reducing conditions. However, reactive oxygen species (ROS) have been shown to induce citrullination of histones in granulocytes. Here we examine the ability of H2O2 and leukocyte-derived ROS to regulate PAD activity using citrullination of fibrinogen as read-out. H2O2 at concentrations above 40?µM inhibited the catalytic activity of PAD2 and PAD4 in a dose-dependent manner. PMA-stimulated leukocytes citrullinated fibrinogen and this citrullination was markedly enhanced when ROS formation was inhibited by the NADPH oxidase inhibitor diphenyleneiodonium (DPI). In contrast, PAD released from stimulated leukocytes was unaffected by exogenously added H2O2 at concentrations up to 1000?µM. The role of ROS in regulating PAD activity may play an important part in preventing hypercitrullination of proteins.

SUBMITTER: Damgaard D 

PROVIDER: S-EPMC6021033 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Reactive oxygen species inhibit catalytic activity of peptidylarginine deiminase.

Damgaard Dres D   Bjørn Mads Emil ME   Jensen Peter Østrup PØ   Nielsen Claus Henrik CH  

Journal of enzyme inhibition and medicinal chemistry 20171201 1


Protein citrullination catalysed by peptidylarginine deiminase (PAD) may play an important pathogenic role in several chronic inflammatory diseases and malignancies. PAD2, PAD4, and citrullinated proteins are found in the synovium of rheumatoid arthritis patients. PAD activity is dependent on calcium and reducing conditions. However, reactive oxygen species (ROS) have been shown to induce citrullination of histones in granulocytes. Here we examine the ability of H<sub>2</sub>O<sub>2</sub> and le  ...[more]

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