Temporal Patterns of Poly(ADP‐Ribose) Polymerase Activation in the Cortex Following Experimental Brain Injury in the Rat
: 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...
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Published in | Journal of neurochemistry Vol. 73; no. 1; pp. 205 - 213 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford UK
Blackwell Science Ltd
01.07.1999
Blackwell |
Subjects | |
Online Access | Get full text |
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Summary: | : 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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Bibliography: | Lippincott Williams & Wilkins, Inc., Philadelphia 3‐AB, 3‐aminobenzamide; BER, base excision repair; FP, fluid percussion; PAR, poly(ADP‐ribose); PARIS, poly(ADP‐ribose) in situ; PARP, poly(ADP‐ribose) polymerase; TBI, traumatic brain injury; TUNEL, terminal‐deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end‐labeling. Abbreviations used ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-3042 1471-4159 |
DOI: | 10.1046/j.1471-4159.1999.0730205.x |