期刊
NEUROBIOLOGY OF AGING
卷 36, 期 7, 页码 2319-2330出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.04.004
关键词
Base excision repair; Stroke; Xrcc1; Oxidative stress
资金
- Intramural Research Program of the National Institutes of Health and National Institute on Aging [AG 000723-07]
- NINDS/NIMH [CA 90073]
- National Multiple Sclerosis Society
- Department of Veterans Affairs
Oxidative DNA damage is mainly repaired by base excision repair (BER). Previously, our laboratory showed that mice lacking the BER glycosylases 8-oxoguanine glycosylase 1 (Ogg1) or nei endonuclease VIII-like 1 (Neil1) recover more poorly from focal ischemic stroke than wild-type mice. Here, a mouse model was used to investigate whether loss of 1 of the 2 alleles of X-ray repair cross-complementing protein 1 (Xrcc1), which encodes a nonenzymatic scaffold protein required for BER, alters recovery from stroke. Ischemia and reperfusion caused higher brain damage and lower functional recovery in Xrcc1(+/-) mice than in wild-type mice. Additionally, a greater percentage of Xrcc1(+/-) mice died as a result of the stroke. Brain samples from human individuals who died of stroke and individuals who died of non-neurological causes were assayed for various steps of BER. Significant losses of thymine glycol incision, abasic endonuclease incision, and single nucleotide incorporation activities were identified, as well as lower expression of XRCC1 and NEIL1 proteins in stroke brains compared with controls. Together, these results suggest that impaired BER is a risk factor in ischemic brain injury and contributes to its recovery. Published by Elsevier Inc.
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