Overexpression of GD3 synthase induces apoptosis of vascular endothelial ECV304 cells through downregulation of Bcl-2

Abstract

The disialoganglioside GD3 plays a major role in proliferation, differentiation, and apoptosis. It has been reported that ganglioside GD3 can induce apoptosis through bcl-2 mediated mitochondrial pathway. However, the relationship between ganglioside GD3 and B-cell/CLL lymphoma 2 (Bcl-2) is not fully understood. In this study, we have demonstrated that the downregulation of Bcl-2 by overexpression of CMP-NeuAc:GM3 alpha-2,8-sialyltransferase (GD3 synthase) results in an accelerated apoptosis in vascular endothelial cells (ECV304), as evidenced by DNA fragmentation and caspase-3 activation. In addition, phosphorylation of AKT and cyclic-AMP responsive element binding protein (CREB) was reduced by GD3 synthase overexpression. Moreover, the activation of CREB as a transcriptional factor was also inhibited, as evidenced by electrophoretic mobility shift assay. Therefore, we conclude that GD3 synthase has an apoptotic effect on ECV304 cells through downregulation of Bcl-2 expression via dephosphorylation of AKT and CREB.