Abstract
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 45Ca 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.
Published Version
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