The effect of hypocapnia (PaCO2 27 mmHg) on CaM kinase IV activity, Bax/,Bcl-2 protein expression and DNA fragmentation in the cerebral cortex of newborn piglets

The present study tests the hypothesis that a PaCO2 of 27 mmHg for 1 hr results in increased neuronal nuclear Ca++/calmodulin-dependent protein kinase IV (CaM kinase IV) activity, pro-apoptotic protein expression and DNA fragmentation in the cerebral cortex of newborn piglets. Hypocapnic (HC) and normocapnic newborn piglets were studied. Tissue levels of ATP and phosphocreatine (PCr) were lower in the HC group. CaM kinase IV activity and Bax protein density were higher in the HC group. Bcl-2 protein density was the same in both groups, resulting in an increased ratio of Bax/Bcl-2 in the HC group. Density of nuclear DNA fragments was greater in the HC group and varied inversely with ATP and PCr levels. We conclude that hypocapnia (PaCO2 27 mmHg) results in increased expression of pro-apoptotic proteins and fragmentation of nuclear DNA in newborn piglets. (C) 2003 Elsevier Ireland Ltd. All rights reserved.