The present study tests the hypothesis that
hyperoxia results in increased
tyrosine phosphorylation of apoptotic
proteins Bcl-2, Bcl-xl, Bax & Bad in the mitochondrial fraction of the cerebral cortex of newborn piglets. Twelve newborn piglets were divided into normoxic [Nx, n = 6], exposed to a FiO(2) of 0.21 for 1 h and hyperoxic [Hyx, n = 6], exposed to FiO(2) of 1.0 for 1 h. PaO(2) in Hyx group was maintained at 400 mmHg while the Nx group was kept at 80 to 100 mmHg. The density (O.D.x mm(2)) of phosphorylated Bcl2
protein on westernblot was 19.3 +/- 3.6 in Nx and 41.5 +/- 18.3 in Hyx, (P < 0.05). The density of phosphorylated
Bcl-xl protein density was 26.9 +/- 7.0 in Nx and 47.9 +/- 2.5 in Hyx, (P < 0.05). Phosphorylated Bax density was 43.5 +/- 5.0 in Nx and 43.3 +/- 5.2 in Hyx. Phosphorylated Bad density was 23.6 +/- 3.9 in Nx, 24.4 +/- 4.7 in Hyx. The data show that during
hyperoxia there is a significant increase in
tyrosine phosphorylation of Bcl2 and Bcl-xl, while the phosphorylation of proapototic
proteins Bax & Bad was not altered. We conclude that
hyperoxia leads to post translational modification of
anti apoptotic proteins Bcl2 and Bcl-xl in cerebral cortical mitochondria. We propose that phosphorylation of Bcl2 will result in loss of its antiapoptotic potential by preventing its dimerization with Bax leading to activation of the
caspase pathway and subsequent neuronal death in the cerebral cortex of the newborn piglets.