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HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage / Owain, Howell

Nature Neuroscience, Volume: 13, Issue: 2, Pages: 180 - 189

Swansea University Author: Owain, Howell

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DOI (Published version): 10.1038/nn.2471

Abstract

Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to g...

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Published in: Nature Neuroscience
Published: 2010
Online Access: http://www.scopus.com/record/display.url?eid=2-s2.0-75549089982&origin=resultslist&sort=plf-f&src=s&st1=howell&st2=o.w&nlo=1&nlr=20&nls=&sid=942755C5CBB33656BBE96DCBEAC4A9AE.iqs8TDG0Wy6BURhzD3nFA%3a122&sot=anl&sdt=aut&sl=33&s=AU-ID%28%22Howell%2c+O.+W.%22+6602393502%29&relpos=12&relpos=12&searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29
URI: https://cronfa.swan.ac.uk/Record/cronfa14216
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spelling 2013-12-13T11:26:16.9915833 v2 14216 2013-02-11 HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage 58c995486fc93a242b987640b692db8c 0000-0003-2157-9157 Owain Howell Owain Howell true false 2013-02-11 BMS Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to glutamate and tumor necrosis factor-α. Nuclear export of HDAC1 was mediated by the interaction with the nuclear receptor CRM-1 and led to impaired mitochondrial transport. The formation of complexes between exported HDAC1 and members of the kinesin family of motor proteins hindered the interaction with cargo molecules, thereby inhibiting mitochondrial movement and inducing localized beading. This effect was prevented by inhibiting HDAC1 nuclear export with leptomycin B, treating neurons with pharmacological inhibitors of HDAC activity or silencing HDAC1 but not other HDAC isoforms. Together these data identify nuclear export of HDAC1 as a critical event for impaired mitochondrial transport in damaged neurons. Journal Article Nature Neuroscience 13 2 180 189 31 12 2010 2010-12-31 10.1038/nn.2471 http://www.scopus.com/record/display.url?eid=2-s2.0-75549089982&amp;origin=resultslist&amp;sort=plf-f&amp;src=s&amp;st1=howell&amp;st2=o.w&amp;nlo=1&amp;nlr=20&amp;nls=&amp;sid=942755C5CBB33656BBE96DCBEAC4A9AE.iqs8TDG0Wy6BURhzD3nFA%3a122&amp;sot=anl&amp;sdt=aut&amp;sl=33&amp;s=AU-ID%28%22Howell%2c+O.+W.%22+6602393502%29&amp;relpos=12&amp;relpos=12&amp;searchTerm=AU-ID%28\%26quot%3BHowell%2C+O.+W.\%26quot%3B+6602393502%29 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2013-12-13T11:26:16.9915833 2013-02-11T18:22:29.9098739 Swansea University Medical School Medicine Jin Young Kim 1 Siming Shen 2 Karen Dietz 3 Ye He 4 Owain Howell 0000-0003-2157-9157 5 Richard Reynolds 6 Patrizia Casaccia 7
title HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
spellingShingle HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
Owain, Howell
title_short HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
title_full HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
title_fullStr HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
title_full_unstemmed HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
title_sort HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage
author_id_str_mv 58c995486fc93a242b987640b692db8c
author_id_fullname_str_mv 58c995486fc93a242b987640b692db8c_***_Owain, Howell
author Owain, Howell
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description Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo models of demyelination and in cultured neurons exposed to glutamate and tumor necrosis factor-α. Nuclear export of HDAC1 was mediated by the interaction with the nuclear receptor CRM-1 and led to impaired mitochondrial transport. The formation of complexes between exported HDAC1 and members of the kinesin family of motor proteins hindered the interaction with cargo molecules, thereby inhibiting mitochondrial movement and inducing localized beading. This effect was prevented by inhibiting HDAC1 nuclear export with leptomycin B, treating neurons with pharmacological inhibitors of HDAC activity or silencing HDAC1 but not other HDAC isoforms. Together these data identify nuclear export of HDAC1 as a critical event for impaired mitochondrial transport in damaged neurons.
published_date 2010-12-31T13:26:58Z
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