SUMO2 3 conjugation is an endogenous neuroprotective mechanism

• Published in: Journal of cerebral blood flow and metabolism Vol. 31; no. 11; pp. 2152 - 2159
• Main Authors: Datwyler, Anna Lena, Lättig-Tünnemann, Gisela, Yang, Wei, Paschen, Wulf, Lee, Sabrina Lin Lin, Dirnagl, Ulrich, Endres, Matthias, Harms, Christoph
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2011; Nature Publishing Group; Sage Publications Ltd
• Subjects: Adenosine Triphosphate - metabolism; Animals; Biological and medical sciences; Brief Communication; Cell Culture Techniques; Cell Hypoxia; Cell Survival - drug effects; Cell Survival - genetics; Cells, Cultured; Genetic Vectors; Glucose - metabolism; Immunohistochemistry; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Ischemic Attack, Transient - prevention & control; Lentivirus - genetics; Medical sciences; Mice; Mice, Inbred C57BL; MicroRNAs - administration & dosage; MicroRNAs - genetics; MicroRNAs - pharmacology; Neurology; Neurons - metabolism; Neurons - pathology; Neuropharmacology; Neuroprotective agent; Oxygen - metabolism; Pharmacology. Drug treatments; Small Ubiquitin-Related Modifier Proteins - genetics; Small Ubiquitin-Related Modifier Proteins - metabolism; Sumoylation - drug effects; Sumoylation - genetics; Ubiquitins - genetics; Ubiquitins - metabolism; Vascular diseases and vascular malformations of the nervous system; lentiviral microRNA delivery; SUMO conjugation; endogenous neuroprotection; oxygen–glucose deprivation; Ubiquitin; Oxygen; Nervous system diseases; Central nervous system disease; Glucose; oxygen-glucose deprivation; Cerebrovascular disease; Cerebral disorder
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2011.112

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.