Ap4A induces apoptosis in human cultured cells
A Vartanian1, I Alexandrov, I Prudowski
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow.
FEBS Letters
|August 19, 1999
Summary
Diadenosine tetraphosphate (Ap4A) induces apoptosis, while diadenosine triphosphate (Ap3A) acts as a co-inductor for cell differentiation, suggesting opposing roles in cellular status regulation.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Signaling
Background:
- Diadenosine oligophosphates (Ap(n)A) are signaling molecules in animal cells.
- The ratio of Ap3A to Ap4A changes with cellular status, differentiation, and interferon treatment.
- Ap3A decreases and Ap4A increases during VP16-induced apoptosis.
Purpose of the Study:
- To investigate the effects of exogenously added Ap3A and Ap4A on apoptosis and cell differentiation.
- To understand the role of Ap4A breakdown in its apoptotic effects.
- To explore the potential synergistic effects of Ap3A with other compounds.
Main Methods:
- Ap(n)A penetration into cells was facilitated by cold shock.
- Ap4A and hydrolysis-resistant analogues were administered to various human and mouse cell lines.
- Ap3A was tested alone and in combination with protein kinase C activators.
Main Results:
- 10 microM Ap4A induced apoptosis in HL60, U937, Jurkat, and VMRO cells.
- Ap4A's apoptotic effect was dependent on its breakdown.
- Ap3A alone did not induce apoptosis or differentiation but synergized with PKC activators to induce differentiation in HL60 cells.
Conclusions:
- Ap4A and Ap3A act as physiological antagonists in regulating cellular status.
- Ap4A induces apoptosis, while Ap3A co-induces differentiation.
- The precise signal transduction mechanisms for these effects remain to be elucidated.
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