Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons.
Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) conjugation is markedly activated in the brain during deep to moderate hypothermia. Animals were subjected to normothermic (37°C) or deep to moderate (18°C, 24°C, 30°C) hypothermic cardiopulmonary bypass, and the effects of hypothermia on SUMO conjugation were evaluated by Western blot and immunohistochemistry. Exposure to moderate 30°C hypothermia was sufficient to markedly increase levels and nuclear accumulation of SUMO2/3-conjugated proteins in these cells. Deep hypothermia induced nuclear translocation of the SUMO-conjugating enzyme Ubc9, suggesting that the increase in nuclear levels of SUMO2/3-conjugated proteins observed in brains of hypothermic animals is an active process. Exposure of primary neuronal cultures to deep hypothermia induced only a moderate rise in levels of SUMO2/3-conjugated proteins. This suggests that neurons in vivo have a higher capacity than neurons in vitro to activate this endogenous potentially neuroprotective pathway upon exposure to hypothermia. Identifying proteins that are SUMO2/3 conjugated during hypothermia could help to design new strategies for preventive and therapeutic interventions to make neurons more resistant to a transient interruption of blood supply.
Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Liangli
L
Wang
Qing
Q
Ma
Wei
W
Yang
G Burkhard
GB
Mackensen
Wulf
W
Paschen
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D005260:Female; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D009687:Nuclear Proteins; C529669:SUMO2 protein, rat; C529670:SUMO3 protein, rat; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9