GW24-e3646 Adiponectin regulates SR Ca2+cycling following ischaemia/reperfusion through sphingosine 1-phosphate-CaMKII signalling in mice

Objectives The circulating, adipocyte-secreted hormone adiponectin (APN) exerts protective effects on the heart under stress conditions. Recent study demonstrated that APN induces a marked Ca 2+ influx in skeletal muscle. However, whether APN modulates [Ca 2+ ] i activity, especially modulates [Ca 2+ ] i transients in cardiomyocytes is still unknown. This study was designed to determine whether and how APN modulates [Ca 2+ ] i transients in cardiomyocytes. Methods Adult male wild-type (WT) and APN knock-out (APN KO) mice were subjected to myocardial ischaemia/reperfusion (I/R, 30 min/30 min) injury.We observed CaMKII-PLB phosphorylation and SR Ca 2+ -ATPase (SERCA2) activity were downregulated in I/R heart of WT mice (all P 2+ transient peaks, and number of Ca 2+ sparks (all P >0.05), but decreased [Ca 2+ ] i transients (P 2+ decay rate (P 2+ ] i transients (P 2+ ] i transients in APN KO myocytes via S1PR1/3 (all P Results Treatment of myocytes after hypoxia/reoxygenation with S1P also increased cell viability and reduced caspase-3 activity and apoptosis (all P Conclusions These data demonstrate that S1P is a novel regulator of SERCA2 by activating CaMKII-PLB signalling and mediates APN-induced cardioprotection.