Glutaminase 1 Promotes the Proliferation of Endothelial Cells via the Induction of Cyclin A

Glutaminase (GLS) is a phosphate-dependent enzyme that converts glutamine to glutamate and ammonia. There are two distinct isoforms of GLS, GLS1 and GLS2, which possess discrete tissue distribution, structural properties, enzyme kinetics, and molecular regulation. Although endothelial cells possess substantial GLS activity, its functional role in these cells remains largely unknown. In the present study, we characterized the expression of GLS in endothelial cells and investigated the effect of GLS on the proliferation of endothelial cells. Human umbilical vein endothelial cells (HUVEC) expressed high levels of GLS1, but GLS2 was not detected in these cells. Treatment of HUVEC with the non-selective GLS inhibitor 6-diazo-5-oxo-L-ornithine or the selective GLS1 inhibitors bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide or CB-839 resulted in a concentration-dependent inhibition of endothelial cell growth. All three GLS1 inhibitors also blocked DNA synthesis in both HUVEC and mouse aortic endothe...