Regulation of ROS Production and Vascular Function by Carbon Monoxide
Figure 2
Effects of CO on targets of ROS generation in endothelial cells. CO binds to cytochrome c oxidase (COX), which is a terminal electron acceptor (complex IV) of the electron transport chain, which changes the redox state of the electron transport chain and produces ROS in mitochondria. CO-dependent mitochondrial superoxide is converted to by SOD2 (Mn-SOD). Stimulation with TNF- and LPS induces the recruitment of Nox2, , and Rac1 into lipid rafts, thereby promoting Nox activation and ROS production. Superoxide interacts with eNOS-derived NO to produce peroxynitrite, which contributes to endothelial dysfunction. Binding of CO to the heme moiety of Nox and eNOS inhibits production of superoxide and NO, respectively.
