title: Role of the O-linked β-N-acetylglucosamine in the cardioprotection induced by isoflurane.
abstract: BACKGROUND
  Cardiac protection by volatile anesthetic-induced preconditioning and ischemic preconditioning have similar signaling pathways. Recently, it was reported that augmentation of protein modified with O-linked β-N-acetylglucosamine (O-GlcNAc) contributes to cardiac protection. This study investigated the role of O-GlcNAc in cardiac protection induced by anesthetic-induced preconditioning.
  
  
  METHODS
  O-GlcNAc-modified proteins were visualized by immunoblotting. Tolerance against ischemia or reperfusion was tested in vivo (n = 8) and in vitro (n = 6). The opening of the mitochondrial permeability transition pore (mPTP) upon oxidative stress was examined in myocytes treated with calcein AM (n = 5). Coimmunoprecipitation and enzymatic labeling were performed to detect the mitochondrial protein responsible for the mPTP opening.
  
  
  RESULTS
  Isoflurane treatment and the consequent augmentation of O-GlcNAc concentrations reduced the infarct size (26 ± 5% [mean ± SD], P < 0.001) compared with the control. The protective effect of O-GlcNAc was eliminated in the group pretreated with the O-GlcNAc transferase inhibitor alloxan (39 ± 5%, P < 0.001). Myocyte survival also showed the same result in vitro. Formation of the mPTP was abrogated in the isoflurane-treated cells (86 ± 4%, P < 0.001) compared with the control and alloxan-plus-isoflurane-treated cells (57 ± 7%, P < 0.001). Coimmunoprecipitation and enzymatic labeling studies revealed that the O-GlcNAc-modified, voltage-dependent anion channel restained the mPTP opening.
  
  
  CONCLUSIONS
  Isoflurane induced O-GlcNAc modification of mitochondrial voltage-dependent anion channel. This modification inhibited the opening of the mPTP and conferred resistance to ischemia-reperfusion stress.
authors.affiliation: Department of Anesthesiology, Support Center for Advanced Medical Sciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Hirose
authors.forename: Yasuo M
authors.initials: YM
authors.lastname: Tsutsumi
authors.forename: Rie
authors.initials: R
authors.lastname: Tsutsumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shono
authors.forename: Erika
authors.initials: E
authors.lastname: Katayama
authors.forename: Michiko
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shuzo
authors.initials: S
authors.lastname: Oshita
mesh_terms: D000117:Acetylglucosamine / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D050994:Voltage-Dependent Anion Channels / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D050994:Voltage-Dependent Anion Channels; D007530:Isoflurane; D000117:Acetylglucosamine