Ischemic preconditioning increases myocardial O-GlcNAc glycosylation

Rebekka Vibjerg Jensen, Jacob Johnsen, Steen Buus Kristiansen, Natasha Elizabeth Zachara, Hans Erik Bøtker

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives. 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. Design. 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.

Original languageEnglish (US)
Pages (from-to)168-174
Number of pages7
JournalScandinavian Cardiovascular Journal
Volume47
Issue number3
DOIs
StatePublished - 2013

Keywords

  • Alloxan
  • Azaserine
  • Ischemia-reperfusion injury
  • Ischemic preconditioning
  • O-GlcNAc

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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