Effect of hypoxia and reoxygenation on the activity of transglutaminase in brain of newborn piglets

The transglutaminase activity in five regions of the brain of newborn piglets was measured and the effects of hypoxia and posthypoxic period on this activity evaluated. Enzyme activity was measured in homogenates from cortex, hippocampus, striatum, thalamus and midbrain. The control activities were 7.2, 6.2, 6.0, 5.7 and 4.6 pmol/mg protein/min, respectively. The activities at the end of an 18 min period of hypoxia induced by an F_iO₂ of 9% were not significantly different from control activities. By 3 h after the hypoxic episode, however, the transglutaminase activities were significantly above control levels in all five regions of the brain. Measurements of the kinetic constants of tranglutaminase indicated that increases in enzyme activity were associated with an increase in Vmax with no significant change in the apparent affinity of the enzyme for the substrate, putrescine. The increased activity of transglutaminase during the posthypoxic period, with no changes immediately after hypoxia, suggest that the increases could be due to increased enzyme synthesis rather then activation of existing enzyme. The rise in transglutaminase activity subsequent to a hypoxic episode may contribute significantly to the long-term disturbances in cellular metabolism in the immature brain induced by hypoxic episodes.