Protein tyrosine nitration of 15-hydroxy prostaglandin dehydrogenase in the human mast cell line LAD2

Mast cells (MC) play a pivotal role in allergic inflammation and nitric oxide (NO) is known to regulate MC function. One mechanism of NO mediated actions is the post-translational modification protein tyrosine nitration mediated by reactive nitrogen species. In this study we identified targets for nitration in the human mast cell line LAD2 after treatment with a nitric oxide donor and with peroxynitrite. Using two dimensional gel electrophoresis and western blot analyses with monoclonal and polyclonal antibodies we identified 15-hydroxy prostaglandin dehydrogenase (PGDH), a major prostaglandin catabolizing enzyme, as a target for nitration in LAD2. This is the first report on expression of this enzyme in MC and also the first report that PGDH is a target of protein tyrosine nitration. Since MC synthesize and metabolize many prostaglandins including prostaglandin E2, the major substrate for PGDH, nitration of this prostaglandin catabolizing enzyme is likely functionally significant.

► 15-Hydroxy prostaglandin dehydrogenase is expressed in human mast cells. ► Nitration of 15-hydroxy prostaglandin dehydrogenase was reported for the first time. ► Peroxynitrite treatment nitrate human 15-hydroxy prostaglandin dehydrogenase. ► Peroxynitrite reduces 15-hydroxy prostaglandin dehydrogenase activity in LAD2.