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.
Wang
X
X
Perinatal Center, Department of Physiology, Göteborg University, Göteborg, Sweden.
Karlsson
J O
JO
Zhu
C
C
Bahr
B A
BA
Hagberg
H
H
Blomgren
K
K
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