CPP32 activation during dolichyl phosphate-induced apoptosis in U937 leukemia cells

FEBS Lett. 1997 Jul 21;412(1):153-6. doi: 10.1016/s0014-5793(97)00763-1.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism
  • Apoptosis*
  • Caspase 3
  • Caspases*
  • Cyclic AMP / metabolism
  • Cysteine Endopeptidases / metabolism*
  • DNA Fragmentation
  • Dideoxyadenosine / analogs & derivatives
  • Dideoxyadenosine / pharmacology
  • Dolichol Phosphates / pharmacology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Enzyme Precursors / metabolism
  • Humans
  • Kinetics
  • Leukemia, Monocytic, Acute / enzymology*
  • Tumor Cells, Cultured

Substances

  • Adenylyl Cyclase Inhibitors
  • Dolichol Phosphates
  • Enzyme Inhibitors
  • Enzyme Precursors
  • dolichol monophosphate
  • 9-(tetrahydro-2-furyl)-adenine
  • Dideoxyadenosine
  • 2',5'-dideoxyadenosine
  • Cyclic AMP
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Adenylyl Cyclases
  • Adenine