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Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway
Journal article   Open access

Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway

Hoon Ryu, Junghee Lee, Beatrix A Olofsson, Aziza Mwidau, Alpaslan Deodoglu, Maria Escudero, Erik Flemington, Jane Azizkhan-Clifford, Robert J Ferrante and Rajiv R Ratan
Proceedings of the National Academy of Sciences - PNAS, v 100(7), pp 4281-4286
01 Apr 2003
PMID: 12640146
url
https://doi.org/10.1073/pnas.0737363100View
Published, Version of Record (VoR) Open

Abstract

Biological Sciences
Oxidative stress is believed to be an important mediator of neurodegeneration. However, the transcriptional pathways induced in neurons by oxidative stress that activate protective gene responses have yet to be fully delineated. We report that the transcription factor Sp1 is acetylated in response to oxidative stress in neurons. Histone deacetylase (HDAC) inhibitors augment Sp1 acetylation, Sp1 DNA binding, and Sp1-dependent gene expression and confer resistance to oxidative stress-induced death in vitro and in vivo . Sp1 activation is necessary for the protective effects of HDAC inhibitors. Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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