Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes.
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.
Ikeda
Yasumasa
Y
Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118, USA.
Ohashi
Koji
K
Shibata
Rei
R
Pimentel
David R
DR
Kihara
Shinji
S
Ouchi
Noriyuki
N
Walsh
Kenneth
K
D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D015428:Myocardial Reperfusion Injury / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000201:enzymology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000502:physiology*; D049349:Receptors, Lysosphingolipid / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D015854:Up-Regulation; D000099157:Sphingosine Kinase
D052242:Adiponectin; D051546:Cyclooxygenase 2; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D000099157:Sphingosine Kinase