The Lysophospholipids Sphingosine-1-Phosphate and Lysophosphatidic Acid Enhance Survival during Hypoxia in Neonatal Rat Cardiac Myocytes

The lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) stimulate cellular proliferation and affect numerous cellular functions by signaling through G protein-coupled endothelial differentiation gene-encoded (Edg) receptors. S1P and LPA also act as survival factors in many cell types, but have not previously been studied in cardiac myocytes. We incubated neonatal rat cardiac myocytes either in room air/1% CO2(normoxia) or in an atmosphere of 99% N2/1%CO2(hypoxia) at 37°C for 18–20 h in the absence of glucose. Cell viability was measured using a calcein ester green fluorescence assay. Under normoxic conditions 88.7±1.0% of the cells were viable after 18–20 h. Severe hypoxia reduced viability to 61.3±4.3% (n=6, P