期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 376, 期 1, 页码 128-133出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.08.108
关键词
HMGB; DNA damage; neurodegeneration; aging; neurodegenerative disease; DNA repair; astrocyte; neuron; Alzheimer's disease; Parkinson's disease; Huntington's disease
资金
- Ministry of Education, Science, Sports and Culture
- Japan Society for the Promotion of Science [16047232, 18500292, 18053007, 16390249, 16650076, 18390254, 18650097, 17025017, 18023014, 20023011]
- Grants-in-Aid for Scientific Research [20023011, 16650076, 18023014, 17025017, 16047232, 16390249, 21390265, 18390254, 18053007, 18500292, 18650097] Funding Source: KAKEN
HMGB1 is an evolutionarily conserved non-histone chromatin-associated protein with key roles in maintenance of nuclear homeostasis; however, the function of HMGB1 in the brain remains largely unknown. Recently, we found that the reduction of nuclear HMGB1 protein level in the nucleus associates with DNA double-strand break (DDSB)-mediated neuronal damage in Huntington's disease [M.L. Qi, K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J Botas, M. Saitoe, E.E. Wanker, H. Okazawa, Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases, Nat. Cell Biol. 9 (2007) 402-414]. In this study, we analyze the region- and cell type-specific changes of HMGB1 and DDSB accumulation during the aging of mouse brain. HMGB1 is localized in the nuclei of neurons and astrocytes, and the protein level changes in various brain regions age-dependently. HMGB1 reduces in neurons, whereas it increases in astrocytes during aging. In contrast, DDSB remarkably accumulates in neurons, but it does not change significantly in astrocytes during aging. These results indicate that HMGB1 expression during aging is differentially regulated between neurons and astrocytes, and suggest that the reduction of nuclear HMGB1 might be causative for DDSB in neurons of the aged brain. (C) 2008 Elsevier Inc. All rights reserved.
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