Furthermore, the ROS-dependent phosphorylation of ERK5 by phosphokinase-C-ζ (PKCζ) and the activation of tumor necrosis factor α (TNFα)- mediated pathway induces the degradation of eNOS leading to the reduced production of NO concentration and in turn contributing further to endothelial dysfunction (34). The gene discussed is TNF; the disease is endothelial dysfunction.