Effect of hyperoxia on cortical neuronal nuclear function and programmed cell death mechanisms.
There is growing concern over detrimental neurologic effects to human newborns caused by increased inspired oxygen concentrations. We hypothesize that hyperoxia (FiO(2)>0.95) results in increased high-affinity Ca(2+)-ATPase activity, Ca(2+)-influx, and proapoptotic protein expression in cortical neuronal nuclei of newborn piglets. Neuronal cerebral energy metabolism was documented by determining ATP and phosphocreatine levels. Neuronal nuclear conjugated dienes and fluorescent compounds were measured as indices of lipid peroxidation. High-affinity Ca(2+)-ATPase activity and ATP-dependent Ca(2+)-influx were determined to document neuronal nuclear membrane function. Hyperoxia resulted in increases in lipid peroxidation, high-affinity Ca(2+)-ATPase activity, ATP-dependent Ca(2+)-influx, and Bax/Bcl-2 ratio in the cortical neuronal nuclei of newborn piglets. We conclude that hyperoxia results in modification of neuronal nuclear membrane function leading to increased nuclear Ca(2+)-influx, and propose that hyperoxia-induced increases in intranuclear Ca(2+) activates the Ca(2+)/calmodulin-dependent protein kinase pathway, triggering increased CREB protein-mediated apoptotic protein expression in hyperoxic neurons.
Chang
Eddie
E
Department of Pediatrics, St. Christopher's Neonatal Research, Drexel University College of Medicine, 245 N. 15th Street, Mail Stop 1029, New College Building, Room 7402, Philadelphia, PA 19102, USA. eddiechangmd@yahoo.com
Hornick
Kristie
K
Fritz
Karen I
KI
Mishra
Om P
OP
Delivoria-Papadopoulos
Maria
M
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology*; D006801:Humans; D018496:Hyperoxia; D015227:Lipid Peroxidation; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013552:Swine; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D010710:Phosphates; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000252:Calcium-Transporting ATPases; D002118:Calcium