title: SUMO2/3 conjugation is an endogenous neuroprotective mechanism.
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.
authors.affiliation: Center for Stroke Research Berlin, Department of Experimental Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Datwyler
authors.forename: Gisela
authors.initials: G
authors.lastname: Lättig-Tünnemann
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Wulf
authors.initials: W
authors.lastname: Paschen
authors.forename: Sabrina Lin Lin
authors.initials: SL
authors.lastname: Lee
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dirnagl
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.forename: Christoph
authors.initials: C
authors.lastname: Harms
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005822:Genetic Vectors; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation / Q000187:drug effects / Q000235:genetics; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C515972:SUMO2 protein, mouse; D025841:Small Ubiquitin-Related Modifier Proteins; C117908:Sumo3 protein, mouse; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen