Abstract
Treatment of U937 cells with dolichyl phosphate led to an increase in the activity of the ICE family protease CPP32, accompanied with cleavage of pre-CPP32 to generate p17. Peptide inhibitors YVAD-cmk and Z-Asp-CH2-DCB (specific to ICE) and DEVD-CHO (specific to CPP32) blocked the dolichyl phosphate-induced apoptosis. The dolichyl phosphate-induced increase of CPP32 activity was inhibited by adenylate cyclase inhibitors, SQ 22536 and 2',5'-dideoxyadenosine. Dolichyl phosphate caused a transient increase of intracellular cAMP concentration. The results suggest that modulation of cAMP synthesis due to the stimulation of adenylate cyclase by dolichyl phosphate plays a critical role in CPP32 activation and apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / analogs & derivatives
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Adenine / pharmacology
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Adenylyl Cyclase Inhibitors
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Adenylyl Cyclases / metabolism
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Apoptosis*
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Caspase 3
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Caspases*
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Cyclic AMP / metabolism
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Cysteine Endopeptidases / metabolism*
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DNA Fragmentation
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Dideoxyadenosine / analogs & derivatives
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Dideoxyadenosine / pharmacology
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Dolichol Phosphates / pharmacology*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Enzyme Precursors / metabolism
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Humans
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Kinetics
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Leukemia, Monocytic, Acute / enzymology*
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Tumor Cells, Cultured
Substances
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Adenylyl Cyclase Inhibitors
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Dolichol Phosphates
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Enzyme Inhibitors
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Enzyme Precursors
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dolichol monophosphate
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9-(tetrahydro-2-furyl)-adenine
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Dideoxyadenosine
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2',5'-dideoxyadenosine
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Cyclic AMP
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CASP3 protein, human
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Caspase 3
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Caspases
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Cysteine Endopeptidases
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Adenylyl Cyclases
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Adenine