Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat

Michelle C. LaPlaca, Ramesh Raghupathi, Ajay Verma, Andrew A. Pieper, Kathryn E. Saatman, Solomon H. Snyder, Tracy K. McIntosh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalJournal of Neurochemistry
Volume73
Issue number1
DOIs
StatePublished - Jul 1 1999

Keywords

  • Apoptosis
  • Caspases
  • DNA repair
  • Nicotinamide adenine dinucleotide
  • Poly(ADP-ribose) polymerase
  • Traumatic brain injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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