Characteristics of the cellular response to oxygen deprivation and subsequent reoxygenation (hypoxia/reoxygenation) include redirection of energy metabolism, increased glucose utilization and expression of oxygen-regulated proteins. Inhibition of protein synthesis during early reoxygenation period prevented effective astrocyte adaptation to hypoxia/reoxygenation, resulting in eventual cell death. To elucidate the role of astrocytes in the central nervous system in response to hypoxia/reoxygenation, we analyzed the cDNA library derived from the cultured rat astrocytes subjected to 24 h of hypoxia followed by reoxygenation by differential display, and isolated a cDNA corresponding to Na/K ATPase alpha1 subunit. The expression of Na/K ATPase alpha1 subunit mRNA as well as beta1subunit mRNA was transiently increased after reoxygenation, whereas hypoxia itself did not induce any gene expression change. Na/K ATPase alpha1 subunit protein was transiently increased, whereas the protein expression for Na/K ATPase beta1 subunit showed sustained induction after reoxygenation. Overexpression of beta1 subunit in HEK 293 cells subjected to hypoxia/reoxygenation promoted survival of the cells. These findings suggest that Na/K ATPases may contribute to maintain the cellular environment of astrocytes subjected to hypoxia/reoxygenation.