The oxidation-reduction reactions in regulation of protein tyrosine phosphatases activity

摘要

Protein Tyrosine Phosphatases (PTPs) serve as key mediators of cell signaling and their activity is strictly related to reactive oxygen species (ROS) level and action. The reversible oxidation is the main mechanism of control of PTPs activity. PTPs are essential enzymes that regulate the tyrosine phosphorylation process which control cell adhesion and migration. Inhibitors of PTP1B can be utilized in a treatment of many disorders associated with its disfunction. Here we analyzed and compared the inhibitory properties against PTP1B of selected PTPs inhibitors, such as hydrogen peroxide, peroctanoic acid and aurintricarboxylic acid (ATA), which decrease the phosphatase activity by oxidation of catalytic cysteine in the active site. We performed as well the spectroscopic studies of potent inhibitor of PTPs, aurintricarboxylic acid. We found that hydrogen peroxide inhibit PTP1B phosphatase with IC_(50) value equal to 200 nM. Peroctanoic acid, which is a product of octanoic acid activated by hydrogen peroxide, is able to inactivate PTP1B with IC_(50) value equal to 50 nM. It is the strongest inhibitor tested but also the most reactive one. Less reactive and still potent inhibitor is ATA with IC_(50) value equal to 100 nM. The spectroscopic studies also confirmed that inhibitory action of ATA is associated with generation of hydrogen peroxide.