Sökning: WFRF:(Curtis Maurice A)
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Epigenetic Regulati...
Epigenetic Regulation of Tissue-Type Plasminogen Activator in Human Brain Tissue and Brain-Derived Cells
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- Olsson, Martina (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics
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- Hultman, Karin, 1980 (författare)
- Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
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Dunoyer-Geindre, Sylvie (författare)
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Curtis, Maurice A (författare)
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Faull, Richard RL (författare)
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Kruithof, Egbert KO (författare)
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- Jern, Christina, 1962 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics
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(creator_code:org_t)
- 2016
- 2016
- Engelska.
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Ingår i: Gene Regulation and Systems Biology. - 1177-6250. ; 10, s. 9-13
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://gup.ub.gu.se...
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https://doi.org/10.4...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The serine protease tissue-type plasminogen activator (t-PA) is involved in both vital physiological brain processes, such as synaptic plasticity, and pathophysiological conditions, such as neurodegeneration and ischemic stroke. Recent data suggest that epigenetic mechanisms play an important role in the regulation of t-PA in human endothelial cells. However, there are limited data on epigenetic regulation of t-PA in human brain-derived cells. We demonstrate that treatment of cultured human neurons and human astrocytes with the histone deacetylase inhibitors trichostatin A (TSA) and MS-275 resulted in a two- to threefold increase in t-PA mRNA and protein expression levels. Next, we performed a chromatin immunoprecipitation assay on treated astrocytes with antibodies directed against acetylated histones H3 and H4 (both markers of gene activation). Treatment with MS-275 and TSA for 24 hours resulted in a significant increase in H3 acetylation, which could explain the observed increase in t-PA gene activity after the inhibition of histone deacety-lation. Furthermore, DNA methylation analysis of cultured human neurons and astrocytes, as well as human postmortem brain tissue, revealed a stretch of unmethylated CpG dinucleotides in the proximal t-PA promoter, whereas more upstream CpGs were highly methylated. Taken together, these results implicate involvement of epigenetic mechanisms in the regulation of t-PA expression in the human brain.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- tissue-type plasminogen activator
- brain tissue
- histone acetylation
- DNA methylation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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