| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Medicine, Division of Cardiology, and Department of Pathology, Albert Einstein College of Medicine, Bronx, New York
Submitted 29 March 2007 ; accepted in final form 13 July 2007
N,N,N-Trimethylsphingosine chloride (TMS), a stable N-methylated synthetic sphingolipid analog, has been shown to modulate protein kinase C (PKC) activity and exert a number of important biological effects, including inhibition of tumor cell growth and metastasis, inhibition of leukocyte migration and respiratory burst, and inhibition of platelet aggregation. We hypothesized that TMS would be cytoprotective in clinically relevant in vivo murine models of myocardial and hepatic ischemia-reperfusion (I/R) injury. Wild-type, obese (ob/ob), and diabetic (db/db) mice were subjected to 30 min of left coronary artery occlusion followed by 24 h of reperfusion in the myocardial I/R model. In additional studies, mice were subjected to 45 min of hepatic artery occlusion followed by 5 h of reperfusion. TMS was administered intravenously at the onset of ischemia. Myocardial infarct size, cardiac function, and serum liver enzymes were measured to assess the extent of tissue injury. TMS attenuated myocardial infarct size by 66% in the wild type and by 36% in the ob/ob mice. Furthermore, TMS reduced serum alanine transaminase levels by 43% in wild-type mice. These benefits did not extend to the ob/ob mice following hepatic I/R or to the db/db mice following both myocardial and hepatic I/R. A likely mechanism is the failure of TMS to inhibit PKC-
translocation in the diseased heart. These data suggest that although TMS is cytoprotective following I/R in normal animals, the cytoprotective actions of TMS are largely attenuated in obese and diabetic animals.
sphingolipids
This article has been cited by other articles:
|
|
 |
|
  J. W. Calvert, D. J. Lefer, S. Gundewar, L. Poston, and W. A. Coetzee Developmental programming resulting from maternal obesity in mice: effects on myocardial ischaemia\#8211;reperfusion injury Exp Physiol, July 1, 2009; 94(7): 805 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Bulhak, C. Jung, C.-G. Ostenson, J. O. Lundberg, P.-O. Sjoquist, and J. Pernow PPAR-{alpha} activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-Kinase/Akt and NO pathway Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H719 - H727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Gundewar, J. W. Calvert, S. Jha, I. Toedt-Pingel, S. Yong Ji, D. Nunez, A. Ramachandran, M. Anaya-Cisneros, R. Tian, and D. J. Lefer Activation of AMP-Activated Protein Kinase by Metformin Improves Left Ventricular Function and Survival in Heart Failure Circ. Res., February 13, 2009; 104(3): 403 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ramachandran, S. Jha, and D. J. Lefer REVIEW Paper: Pathophysiology of Myocardial Reperfusion Injury: The Role of Genetically Engineered Mouse Models Vet. Pathol., September 1, 2008; 45(5): 698 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jha, J. W. Calvert, M. R. Duranski, A. Ramachandran, and D. J. Lefer Hydrogen sulfide attenuates hepatic ischemia-reperfusion injury: role of antioxidant and antiapoptotic signaling Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H801 - H806. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
