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ATP and adenosine prevent via different pathways the activation of caspases in apoptotic AKR-2B fibroblasts

J Hoppe1, R Schäfer, V Hoppe

  • 1Department of Physiological Chemistry, Biozentrum, University of Würzburg Am Hubland, 97074 Würzburg, Germany.

Cell Death and Differentiation
|June 25, 1999
PubMed

Insights

Adenosine triphosphate (ATP) and adenosine protect fibroblasts from serum deprivation-induced cell death via distinct pathways. Both molecules inhibit caspase activation, but their signaling mechanisms, including calcium and cAMP levels, differ significantly.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Fibroblast survival is crucial for tissue homeostasis.
  • Serum deprivation triggers rapid fibroblast disintegration.
  • Understanding protective mechanisms against cell death is vital.

Purpose of the Study:

  • To investigate the protective effects of ATP and adenosine against serum deprivation-induced cell death in AKR-2B fibroblasts.
  • To elucidate the distinct signaling pathways involved in the protective mechanisms of ATP and adenosine.
  • To determine the role of protein synthesis, calcium, cAMP, and kinase activation in these processes.

Main Methods:

  • Serum deprivation of AKR-2B fibroblasts.
  • Treatment with ATP and adenosine and their derivatives.
  • Assessment of cell viability and protein synthesis inhibition (cycloheximide).
  • Measurement of intracellular calcium and cAMP levels.
  • Analysis of MAP-kinase, RSK, and p70S6-kinase phosphorylation.
  • Investigation of protein kinase C (PKC) and Gi-protein involvement (pertussis toxin).
  • Assay of caspase activation (DEVDase and VEIDase).

Main Results:

  • ATP and adenosine significantly protected fibroblasts from serum deprivation-induced death.
  • Protein synthesis is required for the protective effects.
  • ATP and adenosine trigger distinct intracellular signaling cascades.
  • ATP stimulates Ca2+ release and MAP-kinase pathway activation.
  • Adenosine increases cAMP levels and blocks PDGF-BB-induced cell division.
  • Both ATP and adenosine inhibit caspase activation, converging on a common downstream pathway.

Conclusions:

  • ATP and adenosine are potent inhibitors of serum deprivation-induced cell death in fibroblasts.
  • Their protective effects are mediated through distinct, yet converging, signaling pathways.
  • These findings highlight novel therapeutic targets for preventing cell death in various physiological and pathological conditions.

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