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Temporal Patterns of Poly(ADP‐Ribose) Polymerase Activation in the Cortex Following Experimental Brain Injury in the Rat
Author(s) -
LaPlaca Michelle C.,
Raghupathi Ramesh,
Verma Ajay,
Pieper Andrew A.,
Saatman Kathryn E.,
Snyder Solomon H.,
McIntosh Tracy K.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730205.x
Subject(s) - poly adp ribose polymerase , polymerase , ribose , dna repair , dna damage , dna fragmentation , dna polymerase , microbiology and biotechnology , biology , cortex (anatomy) , enzyme , dna , chemistry , apoptosis , biochemistry , programmed cell death , neuroscience
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.