Neonatology · 2001 · 147 citations · 41 references
ApoptosisCell DeathCerebral HiSocial SciencesOxidative StressNeuroinflammationInflammationCerebral Vascular RegulationAutophagyBrain InjuryNeurologyCell SignalingIschemic SyndromeBiochemistryVascular BiologyNeuroprotectionCerebral Blood FlowReperfusion InjuryCell BiologyCaspase-3 ActivationIschemic StrokeNeurophysiologyNeuroscienceImmature BrainMedicine
Caspase-3 is a major effector protease in several apoptotic pathways, but its role in hypoxic-ischemic (HI) brain injury is incompletely understood. Cerebral HI was induced in 7-day-old rats by unilateral carotid artery ligation and exposure to 7.7% oxygen for 55 min. Caspase-3-like activity was significantly increased at 1 h (208%), peaked at 24 h (2,563%) and was still increased 6 days after HI (169%) in the ipsilateral cerebral cortex. Concomitantly, cleavage of the caspase-3 proform (31/33 kD) was detected on immunoblots, producing 29- and 17-kD fragments. Furthermore, significant degradation of the endogenous caspase-3 substrates inhibitor of caspase-activated DNase (DNA fragmentation factor 45), poly(ADP-ribose) polymerase and fodrin occurred. In conclusion, caspase-3 is activated extensively in the immature brain after HI. The subsequent cleavage of proteins involved in cellular homeostasis and repair may contribute to the process of brain injury.
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A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
Masato Enari, Hideki Sakahira, Hideki Yokoyama et al. · Nature · 1998 · 3.2K citations