Laura R Siracusa, Eugene Park, Elaine Liu, Andrew J Baker
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引用次数: 0
Abstract
Under normal physiological conditions high mobility group box protein 1 (HMGB1) stabilizes chromatin, controls transcription, and contributes to DNA repair. Cellular stress or injury results in HMGB1 release from the nucleus acting as a proinflammatory cytokine. The objective of this study was to characterize the temporal progression of nuclear HMGB1 loss up to one week following modeled TBI in 250 g male rats and correlate these changes with the response of DNA damage proteins. HMGB1 was present in the cytoplasm and absent from the nucleus of neurons within 6 h of injury. Quantitative immunohistochemistry and Western blot analysis showed a significant decrease in nuclear HMGB1 expression at 6 and 24 h post-injury compared to controls. Approximately 20 % of neurons were lacking nuclear HMGB1 expression at 7 days post-injury. Cells which were negative for nuclear HMGB1 expression labelled positive for HIF1α, PARP, and γH2AX, indicators of oxidative stress and DNA damage. Nuclear HIF1α expression was detected at 6 h after injury. Nuclear expression of HIF1α, PARP, and γH2AX was observed at 7 days post-injury, suggesting activation of oxidative stress response mechanisms and DNA damage repair pathways. The temporal changes in HMGB1 translocation in conjunction with expression of DNA damage markers suggest a relationship between injury-induced HMGB1 loss in neurons and subsequent DNA damage. These results highlight a potential injury response mechanism with long-term implications in relation to genetic health of surviving neurons.
期刊介绍:
An international multidisciplinary journal devoted to fundamental research in the brain sciences.
Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed.
With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.