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 - 1999

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Poly(ADP-ribose) Polymerases
Brain Injuries
Rats
Brain
Chemical activation
DNA
DNA Repair
Proteolysis
Percussion
Repair
Apoptosis
Fluids
DNA Fragmentation
Enzymes
DNA Damage
Sprague Dawley Rats
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat. / LaPlaca, Michelle C.; Raghupathi, Ramesh; Verma, Ajay; Pieper, Andrew A.; Saatman, Kathryn E.; Snyder, Solomon H; McIntosh, Tracy K.

In: Journal of Neurochemistry, Vol. 73, No. 1, 1999, p. 205-213.

Research output: Contribution to journalArticle

LaPlaca, Michelle C. ; Raghupathi, Ramesh ; Verma, Ajay ; Pieper, Andrew A. ; Saatman, Kathryn E. ; Snyder, Solomon H ; McIntosh, Tracy K. / Temporal patterns of poly(ADP-ribose) polymerase activation in the cortex following experimental brain injury in the rat. In: Journal of Neurochemistry. 1999 ; Vol. 73, No. 1. pp. 205-213.
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