Epac inhibits apoptosis of human leukocytes.
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.
Grandoch
M
M
Institut für Pharmakologie, Universitätsklinikum Essen, 45122 Essen, Germany.
Bujok
V
V
Fleckenstein
D
D
Schmidt
M
M
Fischer
J W
JW
Weber
A-A
AA
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D020298:U937 Cells
D020662:Guanine Nucleotide Exchange Factors; D010975:Platelet Aggregation Inhibitors; C116122:RAPGEF3 protein, human; D013873:Thionucleotides; C055656:8-((4-chlorophenyl)thio)cyclic-3',5'-GMP; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D006152:Cyclic GMP