Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes

Edited by Beat Imhof

Received 21 December 2007; received in revised form 29 February 2008; accepted 3 March 2008. published online 11 March 2008.

Abstract

The adipose-derived plasma protein, adiponectin (APN), has various protective effects on cardiovascular diseases. In this study, we show that endogenous APN is required for full cyclooxygenase-2 (COX-2) induction by ischemia-reperfusion injury in the heart in vivo. In rat neonatal cardiac myocytes, APN-induced COX-2 expression was reduced by treatment with a sphingosine kinase-1 (SphK-1) inhibitor or siRNA targeting SphK-1. Treatment with a sphingosine-1-phosphate (S1P) receptor antagonist also diminished COX-2 expression in response to APN stimulation. These findings suggest that APN is a physiological regulator of COX-2 signaling in the heart and that this regulation occurs in part via a SphK-1–S1P receptor dependent mechanism in cardiac myocytes.

Keywords: Adiponectin, Cyclooxygenase-2, Sphingosine kinase-1, Cardiac myocytes

a Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA

b Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya 466-8550, Japan

c Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, and Myocardial Biology Unit, Boston University School of Medicine, 715 Albany Street, X704, Boston, MA 02118, USA

d Departments of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

Corresponding author. Fax: +1 617 414 2391.

PII: S0014-5793(08)00205-6

doi:10.1016/j.febslet.2008.03.002

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