Abstract
Small ubiquitin-like modifier (SUMO)2/3 but not SUMO1 conjugation is activated after transient cerebral ischemia. To investigate its function, we blocked neuronal SUMO2/3 translation through lentiviral microRNA delivery in primary cortical neurons. Viability was unaffected by SUMO2/3 silencing unless neurons were stressed by transient oxygen-glucose deprivation (OGD). Both 15 and 45 minutes of OGD were tolerated by control microRNA-expressing neurons but damaged >60% of neurons expressing SUMO2/3 microRNA. Damaging OGD (75 minutes) increased neuronal loss to 54% (control microRNA) and to 99% (SUMO2/3 microRNA). This suggests that activation of SUMO2/3 conjugation is an endogenous neuroprotective stress response.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Animals
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Cell Culture Techniques
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Cell Hypoxia
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Cell Survival / drug effects
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Cell Survival / genetics
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Cells, Cultured
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Genetic Vectors
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Glucose / metabolism
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Immunohistochemistry
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Ischemic Attack, Transient / metabolism
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Ischemic Attack, Transient / pathology
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Ischemic Attack, Transient / prevention & control*
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Lentivirus / genetics
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Mice
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Mice, Inbred C57BL
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MicroRNAs / administration & dosage
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MicroRNAs / genetics
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MicroRNAs / pharmacology
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Neurons / metabolism*
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Neurons / pathology
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Oxygen / metabolism
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Small Ubiquitin-Related Modifier Proteins / genetics
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Small Ubiquitin-Related Modifier Proteins / metabolism*
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Sumoylation / drug effects
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Sumoylation / genetics
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Ubiquitins / genetics
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Ubiquitins / metabolism*
Substances
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MicroRNAs
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SUMO2 protein, mouse
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Small Ubiquitin-Related Modifier Proteins
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Sumo3 protein, mouse
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Ubiquitins
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Adenosine Triphosphate
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Glucose
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Oxygen