Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes |
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Authors: | Ikeda Yasumasa Ohashi Koji Shibata Rei Pimentel David R Kihara Shinji Ouchi Noriyuki Walsh Kenneth |
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Institution: | Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA. |
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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. |
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Keywords: | 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 |
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