Premium
Ap 4 A induces apoptosis in human cultured cells
Author(s) -
Vartanian Amalia,
Alexandrov Ivan,
Prudowski Igor,
McLennan Alexander,
Kisselev Lev
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00956-4
Subject(s) - apoptosis , microbiology and biotechnology , jurkat cells , programmed cell death , signal transduction , extracellular , intracellular , chemistry , cellular differentiation , hl60 , biology , biochemistry , t cell , immunology , immune system , gene
Diadenosine oligophosphates (Ap n A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5′,5‴‐P 1 ,P 3 ‐triphosphate to diadenosine 5′,5‴‐P 1 ,P 4 ‐tetraphosphate (Ap 3 A/Ap 4 A) 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 Ap 3 A decreases significantly while that of Ap 4 A increases. Here, we have examined the effects of exogenously added Ap 3 A and Ap 4 A on apoptosis and morphological differentiation. Penetration of Ap n A into cells was achieved by cold shock. Ap 4 A at 10 μM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap 4 A breakdown as hydrolysis‐resistant analogues of Ap 4 A were inactive. On its own, Ap 3 A 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 Ap 4 A and Ap 3 A are physiological antagonists in determination of the cellular status: Ap 4 A induces apoptosis whereas Ap 3 A is a co‐inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.