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Temporal Patterns of Poly(ADP‐Ribose) Polymerase Activation in the Cortex Following Experimental Brain Injury in the Rat
Journal article   Open access   Peer reviewed

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 and Tracy K McIntosh
Journal of neurochemistry, v 73(1)
Jul 1999
DOI: https://doi.org/10.1046/j.1471-4159.1999.0730205.x
PMID: 10386972
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1046/j.1471-4159.1999.0730205.xView
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open

Abstract

Poly(ADP‐ribose) polymerase Nicotinamide adenine dinucleotide Traumatic brain injury Caspases DNA repair Apoptosis
: 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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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