LaPlaca M C, Raghupathi R, Verma A, Pieper A A, Saatman K E, Snyder S H, McIntosh T K
Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
J Neurochem. 1999 Jul;73(1):205-13. doi: 10.1046/j.1471-4159.1999.0730205.x.
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.
聚（ADP - 核糖）聚合酶作为一种DNA碱基切除修复酶，其激活表明存在DNA损伤。该酶在细胞凋亡过程中也会发生位点特异性蛋白水解。由于已知在实验性脑损伤后会发生DNA片段化和细胞凋亡，我们研究了侧方流体冲击脑损伤对聚（ADP - 核糖）聚合酶活性和裂解的影响。雄性Sprague - Dawley大鼠（n = 52）麻醉后，接受中度严重程度（2.5 - 2.8个大气压）的流体冲击脑损伤，并在损伤后30分钟、2小时、6小时、24小时、3天或7天处死。损伤后24小时损伤皮质的基因组DNA发生片段化且能够刺激外源性聚（ADP - 核糖）聚合酶，但损伤后30分钟时未出现这种情况。然而，损伤后30分钟时损伤皮质中的内源性聚（ADP - 核糖）聚合酶活性增强，但随后恢复到基线水平。损伤后前3天在损伤皮质中检测到聚（ADP - 核糖）聚合酶有轻微片段化，但在损伤后7天检测到明显的裂解。综上所述，这些数据表明聚（ADP - 核糖）聚合酶介导的DNA修复在创伤后急性期启动，但随后聚（ADP - 核糖）聚合酶激活未发生，这可能是由于凋亡相关蛋白水解延迟，这可能会损害受损DNA的修复。
