Grandoch M, Bujok V, Fleckenstein D, Schmidt M, Fischer J W, Weber A-A
Institut für Pharmakologie, Universitätsklinikum Essen, 45122 Essen, Germany.
J Leukoc Biol. 2009 Oct;86(4):847-9. doi: 10.1189/jlb.0109048. Epub 2009 Jun 29.
cAMP is known to participate in the regulation of apoptosis in leukocytes. Depending on the cell type, pro- and antiapoptotic effects of cAMP have been described. Thus far, most of the cAMP-dependent effects have been attributed to the activation of PKA. However, Epac proteins (direct cAMP targets and guanine nucleotide exchange factors for Ras-like GTPases) have been shown recently to contribute to cAMP-dependent regulation of apoptosis. Therefore, we investigated the effects of the selective Epac activators 8-pCPT and Sp on apoptosis in human leukocytic cells (U937, HL-60, primary human mononuclear cells). We report here that Epac activation inhibits leukocyte apoptosis significantly.
已知环磷酸腺苷（cAMP）参与白细胞凋亡的调节。根据细胞类型的不同，cAMP的促凋亡和抗凋亡作用均有报道。迄今为止，大多数cAMP依赖性效应都归因于蛋白激酶A（PKA）的激活。然而，最近研究表明，交换蛋白直接激活环磷腺苷（Epac）蛋白（cAMP的直接靶点以及类Ras鸟苷三磷酸酶的鸟嘌呤核苷酸交换因子）有助于cAMP依赖性的凋亡调节。因此，我们研究了选择性Epac激活剂8-对氯苯硫代磷酸腺苷（8-pCPT）和螺内酯（Sp）对人白细胞（U937、HL-60、原代人单核细胞）凋亡的影响。我们在此报告，Epac激活可显著抑制白细胞凋亡。
