PEP-1-SOD1 protects brain from ischemic insult following asphyxial cardiac arrest in rats

Reperfusion following cerebral ischemia leads to excessive production of reactive oxygen species (ROS) and consumption of endogenous antioxidants. Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by ROS. Copper, zinc-superoxide dismutase (SOD1) is one of the major defensive mechanisms by which cells counteract the deleterious effects of ROS after ischemia. However, exogenous SOD1 can not be delivered into living cells because of the poor permeability and selectivity of the cell membrane, thus its application for protecting cells/tissues from oxidative stress damage is greatly limited.

The purified SOD1 or PEP-1-SOD1 fusion proteins were injected into rats via their tail veins, the transduction ability of PEP-1-SOD1 was examined with immunofluorescent staining and SOD1 activity was measured. Moreover, we determined whether or not PEP-1-SOD1 can protect brain from ischemic injury in an experimental asphyxial cardiac arrest rat model through histopathologic analysis, evaluating the levels of malondialdehyde (MDA), S100β and neuron specific enolase (NSE).

SOD1 protein was observed in PEP-1-SOD1-treated animals and SOD1 activity was significantly increased. However, SOD1 protein was not detected in SOD1-treated animals. The transduced PEP-1-SOD1 significantly attenuated cerebral ischemia-reperfusion damage, inhibited ischemia-induced lipid peroxidation, and protected neurons in hippocampus from the damage induced by transient global ischemic insults.

PEP-1-SOD1 fusion protein can be transduced into the neurons in vivo and protect the neurons from the transient global ischemia-induced damage, suggesting PEP-1-SOD1 may be used for the treatment of oxidative stress-associated disorders such as transient global cerebral ischemia.