Biomedical subjects

A Vartanian

Publications and source records attributed to A Vartanian.

6 recordsLinked to original sources

PubMed1999

Ap4A induces apoptosis in human cultured cells.

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.

3T3 Cells↗

PubMed1999

Evaluation of cerebral stresses under acceleration taking into account the lateral ventricles.

In certain flight configurations, fighter pilots are exposed to high Gz acceleration that may induce inflight loss of consciousness (LOC). That LOC is usually preceded by visual prodromes as greyout and blackout. The pathophysiological cause of these phenomena is used to be related to the effects of accelerations on the vascular system (Burton, 1988; Whinnery, 1990). However technological advances have created aircraft generating high accelerations with rapid onset rates (1-6 Gs-1). The symptomatology of inflight LOC has changed and prodromes no longer appear. Pilots also reported a lacunar amnesia of the LOC. In order to evaluate the potentially adverse effect of acceleration on the brain tissue, it was important to study its mechanical behavior under hypergravity. An approximation of the cerebral stresses was obtained by coupling an 'ex vivo' experiment (Guillaume et al., 1997) with a numerical simulation. Firstly, the calculations have been realized considering the brain as homogeneous. Secondly, the cerebral ventricles have been individualized. The results of these two approaches were compared.

Acceleration↗

PubMed1997

Opposite effects of cell differentiation and apoptosis on Ap3A/Ap4A ratio in human cell cultures.

The biological role of diadenosine oligophosphates (DAOP) remains obscure in spite of numerous attempts to solve this enigma. It is known that Ap3A contrary to Ap4A accumulates in human cultured cells treated with interferons (IFNs) alpha or gamma. Since IFNs are considered as antiproliferative regulators, we assumed that different cell status may be associated with varying intracellular levels of DAOP. Promyelocytic human cell line HL60 induced by phorbol ester (TPA) to differentiate to macrophage-like cells in culture exhibits a profound loss of proliferative potential. Here we have shown a 4-5-fold increase in Ap3A concentration in HL60 cells induced by TPA, similar to the effect of IFN, while the Ap4A concentration remained unchanged. On the contrary, in cells undergoing apoptosis induced by VP16, a topoisomerase II inhibitor, the Ap3A concentration considerably decreased, while the Ap4A concentration increased. These findings combined with earlier results suggest an involvement of the Ap3A/Ap4A ratio in signal transduction pathways controlling the cell status.

Apoptosis↗

PubMed1997

c-Raf kinase binds to N-terminal domain of c-Myc.

We have demonstrated that the 50 N-terminal amino acids of c-Myc bind a kinase activity, which phosphorylates Myc in vitro predominantly on Thr8. We also have shown that c-Raf, a widely known Ser/Thr kinase, involved in the Ras signaling pathway, binds to the same portion of c-Myc in vitro. In addition we were able to precipitate native c-Myc/Raf complex from various cell lysates. Physical interaction of Myc and Raf may potentially be a part of their well-known functional cooperation.

Adenosine Triphosphate↗

PubMed1996

Interferons induce accumulation of diadenosine triphosphate (Ap3A) in human cultured cells.

After incubation of human monocytes J96 and human myeloid leukemia HL60 cells with interferons (IFN) alpha or gamma, the Ap3A concentration considerably increases in parallel with accumulation of tryptophanyl-tRNA synthetase (TrpRS, EC 6.1.1.2). The Ap3A formation in response to IFNs is catalysed by an excessive amount of TrpRS. Although the Ap3A function still remains unknown, its accumulation may imply the Ap3A involvement in the IFN-signalling pathway.

Cell Line↗

PubMed1982

[Not Available].

Explore the source record for details and available documents.

France↗