Blocking Tyr265 nitration of protein phosphatase 2A attenuates nitrosative stress–induced endothelial dysfunction in renal microvessels

Protein tyrosine (Tyr) nitration, the covalent addition of a nitro group (•NO2) to Tyr residues, is emerging as a candidate mechanism of endothelial dysfunction. Previous studies have shown that Tyr nitration is primarily induced by nitrosative stress, a process characterized by the production of reactive nitrogen species, especially peroxynitrite anion (ONOO−), which is considered a secondary product of NO in the presence of superoxide radicals (O2•−). However, the impact of nitrosative stress–induced Tyr nitration on endothelial dysfunction has not been thoroughly elucidated to date. We developed an endothelial dysfunction model, a process called “endothelial-to-mesenchymal transition (EndMT),” and evaluated the production of NO, O2•−, and protein nitration during EndMT. The results showed that TGF-β1 stimulation induced EndMT and elevated endothelial NO and O2•− production as well as nitration of the catalytic subunit of protein phosphatase (PP)2A. Mass spectrometry analysis showed that Tyr265 was the ...