Ion Transport Systems as Targets of Free Radicals During Ischemia Reperfusion Injury

Abstract. Oxidative stress is a recognized pathogenic factor in ischemia/reperfu-sion injury (IRI). Iron induced generation of reactive oxygen species (ROS) in vitro reduces both the Na+,K+-ATPase activity and Na+-Ca2+ exchanger of synapto-somal membranes, concomitantly with alteration of physical state of membranes. Oxidative insult also leads to the loss of ability of endoplasmic reticular membranes (ER) to sequester Ca2+ as well as to the increase of Ca2+ permeability. Further-more, ROS induces both lipid peroxidation and lipid-independent modications of membrane proteins. Acute in vivo ischemia alters kinetic parameters of Na+,K+-ATPase aecting mainly the dephosphorylation step of ATPase cycle with parallel changes of Na+-Ca2+ exchanger and alterations of physical membrane environ-ment. Subsequent reperfusion after ischemia is associated with decrease of immuno signal for PMCA 1 isoform in hippocampus. In addition, incubation of non-ischemic membranes with cytosol from ischemic hippocampus decreases level of PMCA 1 in non-ischemic tissues. Loss of PMCA 1 protein is partially protected both by calpain- and by non-specic protease inhibitors which suggest possible activatio