Poly (ADP-ribose) polymerase (PARP) is involved in various cellular functions, including DNA repair, the cell cycle and cell death. While PARP activation could play a critical role in repairing ischemic brain damage, PARP inactivation caused by
caspase 3-cleavage may also be important for apoptotic execution. In this study we investigated the effects of transient global
ischemia and
kainic acid (KA) neurotoxicity, in gerbil and rat brains, respectively, on PARP gene expression and
protein cleavage. PARP
mRNA increased in the dentate gyrus of gerbil brains 4 h after 10 min of global
ischemia, which returned to basal levels 8 h after
ischemia. KA injection (10 mg/kg) also induced a marked elevation in PARP
mRNA level selectively in the dentate gyrus of rat brains 1 h following the injection, which returned to basal levels 4 h after the injection. These observations provide the first evidence of altered PARP gene expression in brains subjected to ischemic and excitotoxic insults. Using both monoclonal and polyclonal
antibodies to PARP cleavage products, little evidence of significant PARP cleavage was found in gerbil brains within the first 3 days after 10 min of global
ischemia. In addition, there was little evidence of significant PARP cleavage in rat brains within 2 days after
kainate (KA) injection. Though these findings show that
caspase induced PARP cleavage is not substantially activated by global
ischemia and excitotoxicity in whole brain, the PARP
mRNA induction could suggest a role for PARP in repairing
DNA following
brain injury.