Hypoxia-induced Ca2+-influx in cerebral cortical neuronal nuclei of newborn piglets.
The present study was designed to investigate the effect of hypoxia on nuclear calcium-influx in the cerebral cortex of newborn piglets. Anesthetized and ventilated newborn piglets divided into normoxic (n=4) and hypoxic groups with varying degrees of tissue hypoxia (n=10) were studied. Nuclear Ca(2+)-influx was determined using (45)Ca(2+) and plotted against ATP and phosphocreatine levels. The plots were analyzed by non-linear regression (exponential) analysis that showed a curvilinear relationship (r=0.92 for ATP and r=0.88 for phosphocreatine). These data suggest a threshold at which there is a sudden increase in the nuclear calcium-influx that then continues to increase with further decrease in the ATP and phosphocreatine levels. The results demonstrate an increase in the nuclear Ca(2+)-influx during hypoxia in newborn piglets and that this increase correlates in a curvilinear fashion with the increase in the degree of cerebral tissue hypoxia. We propose that the hypoxia-induced increase in intranuclear Ca(2+) is due to altered nuclear membrane Ca(2+)-influx mechanisms and will lead to Ca(2+)-mediated alteration of apoptotic gene expression as well as Ca(2+)-dependent activation of endonucleases that result in DNA fragmentation and subsequent programmed neuronal cell death.
Department of Pediatrics, Drexel University College of Medicine and St. Christopher's Hospital for Children, Philadelphia, PA, USA. delivoria@drexel.edu
Maria
M
Delivoria-Papadopoulos
Waseem
W
Akhter
Om P
OP
Mishra
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism*; D013552:Swine
D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D002118:Calcium