TY - JOUR
T1 - Ischemic preconditioning increases myocardial O-GlcNAc glycosylation
AU - Jensen, Rebekka Vibjerg
AU - Johnsen, Jacob
AU - Kristiansen, Steen Buus
AU - Zachara, Natasha Elizabeth
AU - Bøtker, Hans Erik
N1 - Funding Information:
This work was supported by the Danish Research Council (11-108354),The Danish Strategic Research Council (11-1115818), and Institute of Clinical Medicine, Aarhus University, and American Heart Association (SD930162N to N.E.Z) and the National Heart Lung and Blood Institute (R21-HL-108003 and PO1HL107153 to N.E.Z.)
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Alloxan
KW - Azaserine
KW - Ischemia-reperfusion injury
KW - Ischemic preconditioning
KW - O-GlcNAc
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U2 - 10.3109/14017431.2012.756984
DO - 10.3109/14017431.2012.756984
M3 - Article
C2 - 23301939
AN - SCOPUS:84878145030
SN - 1401-7431
VL - 47
SP - 168
EP - 174
JO - Scandinavian Cardiovascular Journal
JF - Scandinavian Cardiovascular Journal
IS - 3
ER -