Hypoxic preconditioning induces neuroprotection against transient global ischemia in adult rats via preserving the activity of Na+/K+-ATPase

We demonstrated previously that 30 min of hypoxic preconditioning (HPC) applied 1 day before 10 min of transient global cerebral ischemia (tGCI) reduced neuronal loss in the hippocampal CA1 subregion in adult rats. The aim of the present study was to investigate the role of Na+/K+-ATPase and protein kinase M zeta (PKM zeta) in the protective effect of HPC against tGCI in adult rats. We found that the activity of Na+/K+-ATPase decreased in the hippocampal CA1 subregion after 10 min of tGCI. This effect was not seen after 30 min of HPC in adult rats. Corresponding to the changes in Na+/K+-ATPase activity, the surface expression of Na+/K+-ATPase alpha 1 subunit increased after HPC. Furthermore, HPC dramatically reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells in the hippocampal CA1 subregion after tGCI. However, neither PKM zeta nor phosphorylation of PKM zeta was changed after tGCI or HPC. The results of the present study are consistent with the hypothesis that both enhanced recovery of Na+/K+-ATPase activity due to preserved the protein levels of Na+/K+-ATPase alpha 1 subunit and reduced DNA fragmentation after tGCI contribute to the protection afforded by HPC. However, PKM zeta activation does not appear to play a role in this neuroprotection. (C) 2011 Elsevier BA,. All rights reserved.