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

Ikeda, Yasumasa; Ohashi, Koji; Shibata, Rei; Pimentel, David R.; Kihara, Shinji; Ouchi, Noriyuki; Walsh, Kenneth

doi:10.1016/j.febslet.2008.03.002

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Volume 582, Issue 7 , Pages 1147-1150, 2 April 2008

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

Edited by Beat Imhof

Yasumasa Ikeda
- Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
Koji Ohashi
- Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
Rei Shibata
- Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
- Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-Ku, Nagoya 466-8550, Japan
David R. Pimentel
- 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
Shinji Kihara
- Departments of Metabolic Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan
Noriyuki Ouchi
- Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
Kenneth Walsh
- Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA
- Corresponding author. Fax: +1 617 414 2391.

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.

Abbreviations: APN, adiponectin, SKI, sphingosine kinase inhibitor, APN-KO, APN-deficient, WT, wild-type, SphK-1, sphingosine kinase-1, S1P, sphingosine-1-phosphate, COX-2, cyclooxygenase-2, AMPK, AMP-activated protein kinase, TNF-α, tumor necrosis factor-α, PG, prostaglandin