Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells.
Hibernation torpor provides an excellent natural model of tolerance to profound reductions in blood flow to the brain and other organs. Here, we report that during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the brain, liver, and kidney. The level of small ubiquitin-related modifier (SUMO) conjugation coincides with the expression level of Ubc9, the SUMO specific E2-conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as markedly as hibernation torpor. Increased SUMO conjugation (induced by Ubc9 overexpression, ischemic preconditioning (PC)+/-hypothermia) was necessary and sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/glucose deprivation (OGD) ('in vitro ischemia'); decreased SUMO conjugation (induced by a dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These data indicate that post-translational modification of proteins by SUMOylation is a prominent feature of hibernation torpor and is critical for cytoprotection by ischemic PC+/-hypothermia in SHSY5Y cells subjected to OGD.
Lee
Yang-ja
YJ
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland 20892-4476, USA.
Miyake
Shin-ichi
S
Wakita
Hideaki
H
McMullen
David C
DC
Azuma
Yoshiaki
Y
Auh
Sungyoung
S
Hallenbeck
John M
JM
D000818:Animals; D001562:Benzimidazoles; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005947:Glucose / Q000172:deficiency; D006605:Hibernation / Q000502:physiology*; D007035:Hypothermia / Q000473:pathology*; D002534:Hypoxia, Brain / Q000503:physiopathology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011419:Propidium; D012589:Sciuridae / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014162:Transfection
D001562:Benzimidazoles; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D011419:Propidium; D005947:Glucose; C017807:bisbenzimide ethoxide trihydrochloride