Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat.
The activation of poly(ADP-ribose) polymerase, a DNA base excision repair enzyme, is indicative of DNA damage. This enzyme also undergoes site-specific proteolysis during apoptosis. Because both DNA fragmentation and apoptosis are known to occur following experimental brain injury, we investigated the effect of lateral fluid percussion brain injury on poly(ADP-ribose) polymerase activity and cleavage. Male Sprague-Dawley rats (n = 52) were anesthetized, subjected to fluid percussion brain injury of moderate severity (2.5-2.8 atm), and killed at 30 min, 2 h, 6 h, 24 h, 3 days, or 7 days postinjury. Genomic DNA from injured cortex at 24 h, but not at 30 min, was both fragmented and able to stimulate exogenous poly(ADP-ribose) polymerase. Endogenous poly(ADP-ribose) polymerase activity, however, was enhanced in the injured cortex at 30 min but subsequently returned to baseline levels. Slight fragmentation of poly(ADP-ribose) polymerase was detected in the injured cortex in the first 3 days following injury, but significant cleavage was detected at 7 days postinjury. Taken together, these data suggest that poly(ADP-ribose) polymerase-mediated DNA repair is initiated in the acute posttraumatic period but that subsequent poly(ADP-ribose) polymerase activation does not occur, possibly owing to delayed apoptosis-associated proteolysis, which may impair the repair of damaged DNA.
LaPlaca
M C
MC
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Raghupathi
R
R
Verma
A
A
Pieper
A A
AA
Saatman
K E
KE
Snyder
S H
SH
McIntosh
T K
TK
D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology*; D004249:DNA Damage; D053938:DNA Fragmentation; D004789:Enzyme Activation; D007700:Kinetics; D008297:Male; D009243:NAD / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009243:NAD; D011065:Poly(ADP-ribose) Polymerases