期刊
SCANDINAVIAN CARDIOVASCULAR JOURNAL
卷 47, 期 3, 页码 168-174出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/14017431.2012.756984
关键词
alloxan; azaserine; O-GlcNAc; ischemic preconditioning; ischemia-repofusion injury
资金
- Danish Research Council [11-108354]
- Danish Strategic Research Council [11-1115818]
- Institute of Clinical Medicine
- Aarhus University
- American Heart Association [SD930162N]
- National Heart Lung and Blood Institute [R21-HL-108003, PO1HL107153]
- Novo Nordisk Fonden [NNF13OC0007447] Funding Source: researchfish
Objectives. Through the hexosamine biosynthetic pathway (HBP) proteins are modified by O-linked-beta-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.
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