Ischemia-induced ribosomal protein S3 expressional changes and the neuroprotective effect against experimental cerebral ischemic damage

Abstract

Some ribosomal proteins are important regulators of development and DNA repair. However, few studies have been conducted on ribosomal protein S3 (rpS3) in the ischemic hippocampus. In the present study, we investigated ischemia-induced changes in rpS3 immunoreactivity, rpS3 mRNA, and protein levels in the hippocampal CA1 region of Mongolian gerbil after 5 min of transient forebrain ischemia. RpS3 immunoreactivity and its protein level were found to be significantly elevated at 6 hr after ischemia/reperfusion and then continuously decreased with time. RT-PCR analysis also showed that rpS3 mRNA levels were significantly elevated in CA1 at 6 hr after transient ischemia. In addition, during the course of this study, we developed a delivery vector (Pep-1) and its rpS3 fusion protein (Pep-1-rpS3) to elucidate the role of rpS3 in ischemia-induced damage. Pep-1-rpS3 administration to ischernic animals significantly and dose dependently increased neuronal survival in the stratum pyramidale of CA1. Moreover, Pep-1-rpS3 treatment reduced terminal deoxynucleotidyl dUTP nick-end labeling-positive CA1 pyramidal cell numbers in the stratum pyramidale. To elucidate how Pep-1-rpS3 ameliorates ischemic damage, changes in 4-hydroxy-2-nonnenal (HNE; an indicator of lipid peroxidation) immunoreactivity and protein levels were investigated. HNE levels and immunoreactivities in Pep-1-rpS3-treated ischernic animals were lower than in corresponding Pep-1-treated ischernic animals. These results indicate that rpS3 has a neuroprotective effect in the brain exposed to ischemia. (c) 2008 Wiley-Liss, Inc.