Molecular and Cellular Biochemistry

, Volume 315, Issue 1–2, pp 179–184 | Cite as

Leptin modulates the negative inotropic effect of interleukin-1β in cardiac myocytes

  • M. Judith Radin
  • Bethany J. Holycross
  • Cristian Dumitrescu
  • Robert Kelley
  • Ruth A. Altschuld
Article

Abstract

Interleukin-1β (IL-1β) is a potent negative inotrope implicated in the functional abnormalities of heart failure. Because the adipokine, leptin, protects against some of the cardiovascular effects of endotoxin, we hypothesized that leptin may modulate the cardiosuppressive effects of IL-1β in isolated cardiomyocytes. Ventricular cardiac myocytes isolated from adult male Sprague Dawley rats were analyzed simultaneously for electrically stimulated contractility and calcium transients following 30 min exposure to IL-1β (10 ng/ml) with or without 60 min pretreatment with leptin (25 ng/ml). IL-1β decreased cell shortening, depressed maximal velocities of shortening and relengthening, and prolonged the time to 90% relaxation. The change in fura2-AM fluorescence ratio amplitude (Δ[Ca2+]) was significantly depressed and the time to return to baseline [Ca2+] was prolonged. The negative inotropic effects of IL-1β were blocked by the neutral sphingomyelinase inhibitor Manumycin A (5 μM) or the ceramidase inhibitor N-oleoyl ethanolamine (1 μM). Prior exposure of myocytes to leptin blocked IL-1β-induced cardiosuppression in conjunction with a blunting of IL-1β stimulated ceramide accumulation. These data suggest that leptin may modulate IL-1β signaling through the sphingolipid signaling pathway in cardiomyocytes.

Keywords

Leptin Interleukin-1β Cardiac myocytes Ceramide 

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • M. Judith Radin
    • 1
  • Bethany J. Holycross
    • 2
  • Cristian Dumitrescu
    • 2
  • Robert Kelley
    • 2
  • Ruth A. Altschuld
    • 3
  1. 1.Department of Veterinary BiosciencesThe Ohio State UniversityColumbusUSA
  2. 2.The Dorothy M. Davis Heart and Lung Research InstituteThe Ohio State UniversityColumbusUSA
  3. 3.Department of Molecular and Cellular BiochemistryThe Ohio State UniversityColumbusUSA

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