Ceramide-induced preconditioning involves reactive oxygen species.
BACKGROUND
Ceramide induces programmed cell death and it is thought to contribute to cardiac ischemia/reperfusion (I/R) injury. In contrast, we have demonstrated that administration of low doses of ceramide engenders cardiac preconditioning (PC). Ceramide is known to generate reactive oxygen species (ROS) in cells. Since mechanisms triggering the ceramide-induced cardioprotection remain unknown, we investigated the role of ROS in the genesis of this protective mechanism.


METHODS
Using an isolated Langendorff-perfused rat heart model, four groups (n > or = 6 in each group) were considered: Control hearts underwent 30 min index regional ischemia and 120 min of reperfusion. In the ceramide group, hearts were preconditioned with c2-ceramide 1 microM for 7 min followed by 10 min washout prior to the I/R insult. In additional groups, MPG (1 mM), a synthetic antioxidant was given for 15 min alone or bracketing the ceramide perfusion. In each group, infarct size was determined at the end of the reperfusion period and superoxide dismutases (CuZnSOD and MnSOD) and catalase activities were evaluated.


RESULTS
Ceramide preconditioning reduced the infarct/area at risk (I/AAR) ratio (8.3 +/- 1.1% for ceramide vs. 36.4 +/- 1.2% for control, p < 0.001). Perfusion with MPG abolished the preconditioning effect of ceramide (I/AAR ratio = 36.7 +/- 4.9%). Ceramide was also associated with a 29% and 38% increase in catalase and CuZnSOD activities, respectively, compared with control group.


CONCLUSIONS
Production of reactive oxygen species following ceramide preconditioning of the ischemic-reperfused heart appears to play a role in the cardioprotective effect of ceramide.
Lecour
Sandrine
S
Hatter Institute for Cardiology Research, Department of Medicine, University of Cape Town Medical School, Cape Town, South Africa. Sandrine@capeheart.uct.ac.za
Owira
Peter
P
Opie
Lionel H
LH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D008625:Tiopronin / Q000494:pharmacology
D000975:Antioxidants; C064769:N-acetylsphingosine; D017382:Reactive Oxygen Species; D008625:Tiopronin; D002374:Catalase; D013482:Superoxide Dismutase; D013110:Sphingosine