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Overexpression of GD3 synthase induces apoptosis of vascular endothelial ECV304 cells through downregulation of Bcl‐2
Author(s) -
Ha Ki-Tae,
Lee Young-Choon,
Kim Cheorl-Ho
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.05.020
Subject(s) - downregulation and upregulation , creb , apoptosis , dephosphorylation , protein kinase b , microbiology and biotechnology , chemistry , phosphorylation , biology , transcription factor , biochemistry , phosphatase , gene
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 α‐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.