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Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage
We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189225/ https://www.ncbi.nlm.nih.gov/pubmed/22016779 http://dx.doi.org/10.1371/journal.pone.0025852 |
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author | Lee, Yang-ja Mou, Yongshan Maric, Dragan Klimanis, Dace Auh, Sungyoung Hallenbeck, John M. |
author_facet | Lee, Yang-ja Mou, Yongshan Maric, Dragan Klimanis, Dace Auh, Sungyoung Hallenbeck, John M. |
author_sort | Lee, Yang-ja |
collection | PubMed |
description | We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent) up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3) conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia. |
format | Online Article Text |
id | pubmed-3189225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31892252011-10-20 Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage Lee, Yang-ja Mou, Yongshan Maric, Dragan Klimanis, Dace Auh, Sungyoung Hallenbeck, John M. PLoS One Research Article We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent) up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3) conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia. Public Library of Science 2011-10-07 /pmc/articles/PMC3189225/ /pubmed/22016779 http://dx.doi.org/10.1371/journal.pone.0025852 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Lee, Yang-ja Mou, Yongshan Maric, Dragan Klimanis, Dace Auh, Sungyoung Hallenbeck, John M. Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title | Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title_full | Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title_fullStr | Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title_full_unstemmed | Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title_short | Elevated Global SUMOylation in Ubc9 Transgenic Mice Protects Their Brains against Focal Cerebral Ischemic Damage |
title_sort | elevated global sumoylation in ubc9 transgenic mice protects their brains against focal cerebral ischemic damage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189225/ https://www.ncbi.nlm.nih.gov/pubmed/22016779 http://dx.doi.org/10.1371/journal.pone.0025852 |
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