Tyrosine phosphorylation of apoptotic proteins during hyperoxia in mitochondria of the cerebral cortex of newborn piglets.
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.
Mudduluru
Manjula
M
Department of Pediatrics, St. Christopher's Hospital for Children, Drexel University College of Medicine, 245 N 15th Street, New College Building, Rm 7410, Mail stop 1029, Philadelphia, PA 19102, USA.
Zubrow
Alan B
AB
Ashraf
Q M
QM
Delivoria-Papadopoulos
Maria
M
Mishra
Om P
OP
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013552:Swine; D014443:Tyrosine / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D014443:Tyrosine