title: Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells.
abstract: 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.
authors.affiliation: Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland 20892-4476, USA.
authors.forename: Yang-ja
authors.initials: YJ
authors.lastname: Lee
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyake
authors.forename: Hideaki
authors.initials: H
authors.lastname: Wakita
authors.forename: David C
authors.initials: DC
authors.lastname: McMullen
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Azuma
authors.forename: Sungyoung
authors.initials: S
authors.lastname: Auh
authors.forename: John M
authors.initials: JM
authors.lastname: Hallenbeck
mesh_terms: 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
chemical_list: D001562:Benzimidazoles; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D011419:Propidium; D005947:Glucose; C017807:bisbenzimide ethoxide trihydrochloride