Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice
- 주제(키워드) Hyperoxygenation , Beta-amyloid , MeCP2 , MMP-2 , MMP-9
- 주제(기타) Medicine, Research & Experimental; Neurosciences
- 설명문(일반) [Choi, Juli; Kwon, Hyejin; Han, Pyung-Lim] Ewha Womans Univ, Dept Brain & Cognit Sci, Seoul 03760, South Korea; [Han, Pyung-Lim] Ewha Womans Univ, Dept Chem & Nano Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- OA유형 Green Published, gold
- 발행기관 KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183555
- 본문언어 영어
- Published As http://dx.doi.org/10.5607/en21014
- PubMed https://pubmed.ncbi.nlm.nih.gov/34483143
초록/요약
Recently we reported that hyperoxygenation treatment reduces amyloid-beta accumulation and rescues cognitive impairment in the Tg-APP/PS1 mouse model of Alzheimer's disease. In the present study, we continue to investigate the mechanism by which hyperoxygenation reduces amyloidbeta deposition in the brain. Hyperoxygenation treatment induces upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue plasminogen activator (tPA), the endopeptidases that can degrade amyloid-beta, in the hippocampus of Tg-APP/PS1 mice. The promoter regions of the three proteinase genes all contain potential binding sites for MeCP2 and Pea3, which are upregulated in the hippocampus after hyperoxygenation. Hyperoxygenation treatment in HT22 neuronal cells increases MeCP2 but not Pea3 expression. In HT22 cells, siRNA-mediated knockdown of Mecp2 decreases Mmp-9 expression and to a lesser extent, Mmp-2 and tPA expression. In mice, siRNA-mediated Mecp2 knockdown in the hippocampus reduces Mmp-9 expression, but not significantlyMmp-2 and tPA expression. The ChIP assay indicates that hyperoxygenation treatment in Tg-APP/PS1 mice increases MeCP2 binding to the promoter regions of Mmp-2, Mmp-9 and tPA genes in the hippocampus. Together, these results suggest that hyperoxygenation increases the expression of MMP-2, MMP-9, and tPA, of which MMP-9 is upregulated via MeCP2 in neuronal cells, and MMP-2 and tPA are upregulated through MeCP2 and other nuclear factors.
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