Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins

Eur J Pharmacol. 2009 Jun 24;613(1-3):93-9. doi: 10.1016/j.ejphar.2009.04.012. Epub 2009 Apr 17.


The modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is increasingly recognized as an important posttranslational modification that modulates cellular function. Recent studies suggested that augmentation of O-GlcNAc levels increase cell survival following stress. Salidroside, one of the active components of Rhodiola rosea, shows potent anti-hypoxia property. In the present study, we reported the cardioprotection of salidroside from ischemia and reperfusion. Cardiomyocytes were exposed to 4 h of ischemia and 16 h of reperfusion, and then cell viability, apoptosis, glucose uptake, ATP levels and cytosolic Ca(2+) concentration were determined, and O-GlcNAc levels were assessed by Western blotting. Salidroside (80 uM) was added 24 h before ischemia/reperfusion was induced. Treatment with salidroside markedly improved cell viability from 64.7+/-4.5% to 85.8+/-3.1%, decreased lactate dehydrogenase (LDH) release from 38.5+/-2.1% to 21.2+/-1.7%, reduced cell apoptosis from 27.2+/-3.2% to 12.2+/-1.9%, significantly improved cardiomyocytes glucose uptake by 1.7-fold and increased O-GlcNAc levels by 1.6-fold, as well as reducing cytosolic Ca(2+) concentration compared to untreated cells following ischemia/reperfusion. Furthermore, the improved cell survival and the increase in O-GlcNAc with salidroside were attenuated by alloxan, an inhibitor of O-GlcNAc transferase. These results suggested that salidroside significantly enhances glucose uptake and increases protein O-GlcNAc levels and this is associated with decreased cardiomyocytes injury following ischemia/reperfusion.

MeSH terms

  • Acetylglucosamine / metabolism*
  • Adenosine Triphosphate / metabolism
  • Alloxan / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Biological Transport / drug effects
  • Calcium / metabolism
  • Cardiotonic Agents / pharmacology*
  • Cell Survival / drug effects
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Glucose / metabolism
  • Glucosides / pharmacology*
  • In Vitro Techniques
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • N-Acetylglucosaminyltransferases / antagonists & inhibitors
  • Phenols / pharmacology*
  • Proteins / metabolism*
  • Rats
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*


  • Cardiotonic Agents
  • Glucosides
  • Phenols
  • Proteins
  • Alloxan
  • Adenosine Triphosphate
  • N-Acetylglucosaminyltransferases
  • N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase
  • Glucose
  • rhodioloside
  • Calcium
  • Acetylglucosamine