FIG. 8.
Scheme for intracellular generation of reactive oxygen species (ROS) and the role of Prdx6. O2•− is dismutated to H2O2, which can generate •OH in the presence of Fe2+. •OH is a powerful oxidant that can peroxidize cell membrane phospholipids (PL). Thus, cell resistance to oxidant stress and repair depends in large part on removal of H2O2 and reduction of phospholipid hydroperoxides (there is no specific scavenger for •OH). H2O2 can be removed by multiple enzymes, including catalase, GSH peroxidases, and all Prdxs. Phospholipid hydroperoxides (PLOOH) are reduced in lung cells by Prdx6; GPx4 represents an alternate enzyme for reduction in some cells (not shown). The product of Prdx6 activity, the hydroxy phospholipid (PLOH), is further reduced by unspecified enzymes to regenerate the native phospholipid. Modified from Manevich and Fisher (53).