TY - JOUR
T1 - Reduction of the DNA base excision repair protein, XRCC1, may contribute to DNA fragmentation after cold injury-induced brain trauma in mice
AU - Fujimura, Miki
AU - Morita-Fujimura, Yuiko
AU - Noshita, Nobuo
AU - Yoshimoto, Takashi
AU - Chan, Pak H.
N1 - Funding Information:
The authors are grateful to Ms. Cheryl Christensen for her editorial assistance and Ms. Liza Reola, Mr. Bernard Calagui and Ms. Jane O. Kim for their technical assistance. This study was supported by National Institutes of Health grants NS14543, NS25372, NS36147 and NO1NS82386. P.H.C. is a recipient of the Jacob Javits Neuroscience Investigator Award.
PY - 2000/6/30
Y1 - 2000/6/30
N2 - 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 β. 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. Theme: Disorders of the nervous system. Topic: Trauma. Copyright (C) 2000 Elsevier Science B.V.
AB - 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 β. 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. Theme: Disorders of the nervous system. Topic: Trauma. Copyright (C) 2000 Elsevier Science B.V.
KW - Apoptosis
KW - Cold injury
KW - DNA base excision repair
KW - Traumatic brain injury
KW - XRCC1
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U2 - 10.1016/S0006-8993(00)02375-1
DO - 10.1016/S0006-8993(00)02375-1
M3 - Article
C2 - 10865064
AN - SCOPUS:0034733983
VL - 869
SP - 105
EP - 111
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -