Implication of altered proteasome function in alcoholic liver injury

Figure 2 The proposed effects of EtOH metabolism on IFNγ-induced STAT1 phosphorylation in VL-17A cells. EtOH is metabolized by ADH and CYP2E1 to Ach and ROS/RNS and increase a formation of PN (peroxynitrite, ONOO^-), a reaction product of O₂^- and NO, which at high concentrations blocks proteasome function. This causes stabilization of SOCS1, a negative regulator of Jak-STAT1 signaling as well as prevents STAT1 phosphorylation on tyrosine residues.