Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkage to cellular proteins.
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.
Wu
Tiejun
T
Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
Zhou
Heping
H
Jin
Zhenxiao
Z
Bi
Shenghui
S
Yang
Xiuling
X
Yi
Dinghua
D
Liu
Weiyong
W
D000117:Acetylglucosamine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors; D010636:Phenols / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*
D002316:Cardiotonic Agents; D005960:Glucosides; D010636:Phenols; D011506:Proteins; D000496:Alloxan; D000255:Adenosine Triphosphate; D017351:N-Acetylglucosaminyltransferases; C037649:N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase; D005947:Glucose; C009172:rhodioloside; D002118:Calcium; D000117:Acetylglucosamine