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Ischemic preconditioning increases myocardial O-GlcNAc glycosylation.
MedLine Citation:
PMID:  23301939     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Rebekka Vibjerg Jensen; Jacob Johnsen; Steen Buus Kristiansen; Natasha Elizabeth Zachara; Hans Erik Bøtker
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  Scandinavian cardiovascular journal : SCJ     Volume:  -     ISSN:  1651-2006     ISO Abbreviation:  Scand. Cardiovasc. J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708377     Medline TA:  Scand Cardiovasc J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Cardiology, Aarhus University Hospital , Skejby, Aarhus N , Denmark.
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