Abstract
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.
MeSH terms
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Apoptosis / drug effects
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Apoptosis / physiology*
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Cyclic AMP / immunology
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / immunology
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Cyclic GMP / analogs & derivatives
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Cyclic GMP / pharmacology
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Guanine Nucleotide Exchange Factors / immunology
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Guanine Nucleotide Exchange Factors / metabolism*
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HL-60 Cells
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Humans
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism*
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Platelet Aggregation Inhibitors / pharmacology
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Thionucleotides / pharmacology
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U937 Cells
Substances
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Guanine Nucleotide Exchange Factors
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Platelet Aggregation Inhibitors
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RAPGEF3 protein, human
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Thionucleotides
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8-((4-chlorophenyl)thio)cyclic-3',5'-GMP
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Cyclic GMP