title: Ischemic preconditioning increases myocardial O-GlcNAc glycosylation.
abstract: OBJECTIVE
  Through the hexosamine biosynthetic pathway (HBP) proteins are modified by O-linked-β-N-acetylglucosamine (O-GlcNAc), which acts as a stress sensor. Augmentation of O-GlcNAc confers cardioprotection against ischemia- reperfusion injury, but its role in ischemic preconditioning (IPC) is unknown. Azaserine and alloxan are unspecific blockers of the HBP and have been used to block the cardioprotective effects of O-GlcNAc. We hypothesized that IPC reduces infarct size and increases O-GlcNAc levels in hearts subjected to ischemia-reperfusion injury, and that these effects could be blocked by azaserine and alloxan.
  
  
  METHODS
  Isolated rat hearts subjected to 40 min global ischemia and 120 min reperfusion were randomized to control, IPC, IPC + azaserine or alloxan, or control + azaserine or alloxan. The effects on infarct size, hemodynamic recovery, myocardial O-GlcNAc levels, and HBP enzyme activities were determined.
  
  
  RESULTS
  IPC reduced infarct size, increased O-GlcNAc levels, O-GlcNAc-transferase levels, and O-GlcNAc-transferase activity. Azaserine and alloxan did not block the effect of IPC on O-GlcNAc levels and O-GlcNAc-transferase activity.
  
  
  CONCLUSIONS
  IPC increased O-GlcNAc levels though increased O-GlcNAc-transferase expression and activity. Azaserine and alloxan failed to block these effects presumably due to poor specificity and sensitivity of the blockers, and IPC-mediated cardioprotection may therefore still be dependent on O-GlcNAc.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus N, Denmark. Rebekka.vibjerg@ki.au.dk
authors.forename: Rebekka
authors.initials: R
authors.lastname: Vibjerg Jensen
authors.forename: Jacob
authors.initials: J
authors.lastname: Johnsen
authors.forename: Steen
authors.initials: S
authors.lastname: Buus Kristiansen
authors.forename: Natasha Elizabeth
authors.initials: NE
authors.lastname: Zachara
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001377:Azaserine / Q000494:pharmacology; D004195:Disease Models, Animal; D006031:Glycosylation; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000496:Alloxan; D001377:Azaserine; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine