PMID- 10452553
OWN - NLM
STAT- MEDLINE
DCOM- 19990909
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 456
IP  - 1
DP  - 1999 Jul 30
TI  - Ap4A induces apoptosis in human cultured cells.
PG  - 175-80
AB  - Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and
      extracellular signaling molecules in animal cells. The ratio of diadenosine
      5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate
      (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells
      undergo differentiation or are treated with interferons. In cells undergoing
      apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of
      Ap3A decreases significantly while that of Ap4A increases. Here, we have examined
      the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological
      differentiation. Penetration of Ap(n)A into cells was achieved by cold shock.
      Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat
      cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as 
      hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced
      neither apoptosis nor cell differentiation but did display strong synergism with 
      the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and
      12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60
      cells. We propose that Ap4A and Ap3A are physiological antagonists in
      determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a
      co-inductor of differentiation. In both cases, the mechanism of signal
      transduction remains unknown.
FAU - Vartanian, A
AU  - Vartanian A
AD  - Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow.
FAU - Alexandrov, I
AU  - Alexandrov I
FAU - Prudowski, I
AU  - Prudowski I
FAU - McLennan, A
AU  - McLennan A
FAU - Kisselev, L
AU  - Kisselev L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Ceramides)
RN  - 0 (Dinucleoside Phosphates)
RN  - 0 (Phorbol Esters)
RN  - 4201-58-5 (N-palmitoylsphingosine)
RN  - 5542-28-9 (diadenosine tetraphosphate)
RN  - 56432-02-1 (diadenosine triphosphate)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NGZ37HRE42 (Sphingosine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - 3T3 Cells/drug effects/pathology
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Cell Differentiation/drug effects
MH  - Cell Membrane Permeability/drug effects/physiology
MH  - Cells, Cultured
MH  - *Ceramides
MH  - DNA/biosynthesis/drug effects
MH  - Dinucleoside Phosphates/metabolism/*pharmacology
MH  - Humans
MH  - Leukemia, Myeloid/drug therapy/pathology
MH  - Mice
MH  - Phorbol Esters/pharmacology
MH  - Protein Kinase C/drug effects
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Tumor Cells, Cultured/drug effects
EDAT- 1999/08/19 00:00
MHDA- 1999/08/19 00:01
CRDT- 1999/08/19 00:00
PHST- 1999/08/19 00:00 [pubmed]
PHST- 1999/08/19 00:01 [medline]
PHST- 1999/08/19 00:00 [entrez]
AID - S0014-5793(99)00956-4 [pii]
AID - 10.1016/s0014-5793(99)00956-4 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Jul 30;456(1):175-80. doi: 10.1016/s0014-5793(99)00956-4.