Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice.
The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase beta. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after cold injury-induced brain trauma (CIBT) in mice, in which apoptosis is assumed to participate. Immunohistochemistry showed the nuclear expression of XRCC1 in the entire region of the control brains. Fifteen minutes after CIBT, nuclear immunoreactivity was predominantly decreased in the inner boundary of the lesion, followed by a significant reduction of XRCC1 in the entire lesion 4 h after CIBT. A characteristic 70-kDa band was detected in the non-traumatic area, and was markedly decreased after CIBT as shown by Western blot analysis. DNA fragmentation was also observed after CIBT, and double staining with XRCC1 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed a spatial relationship between XRCC1 loss and DNA fragmentation 24 h after CIBT. These data indicate that early decrease of XRCC1 and failure of the DNA repair mechanism may contribute to DNA-damaged neuronal cell death after CIBT.
Fujimura
M
M
Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Morita-Fujimura
Y
Y
Noshita
N
N
Yoshimoto
T
T
Chan
P H
PH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001930:Brain Injuries / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D003080:Cold Temperature / Q000009:adverse effects; D053938:DNA Fragmentation / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004487:Edema / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619352:Xrcc1 protein, mouse