Caspase-3 activation after neonatal rat cerebral hypoxia-ischemia.
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.
Perinatal Center, Department of Physiology, Göteborg University, Göteborg, Sweden.
X
X
Wang
J O
JO
Karlsson
C
C
Zhu
B A
BA
Bahr
H
H
Hagberg
K
K
Blomgren
D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins; D002339:Carotid Arteries / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology*; D015151:Immunoblotting; D008026:Ligation; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage; D010446:Peptide Fragments / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013049:Spectrin
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D053148:Caspase 3; D020169:Caspases; D004791:Enzyme Inhibitors; D008840:Microfilament Proteins; D010100:Oxygen; D010446:Peptide Fragments; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins; D013049:Spectrin; C109664:caspase-activated DNase inhibitor; C505410:Casp3 protein, rat