New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo

Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that the peptide up-regulation of all three enzymes appears to be a coordinated process which occurs in vitro and in vivo. We also found that ischemia alone, without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX. This suggests that the CNS can initiate its own “defense” against ROS and FR. Thus, our peptides may activate such systems, as well as AP-1 transcription factor, reported in earlier findings to lead to “repair” (growth) of injured cells.