Interaction of tigliane and daphnane diterpenoid esters with protein kinase C isozymes in vitro

Different biological effects elicited by different phorbol esters in mammalian cells are thought to be due mainly to their differential interaction with, and modification of, the cellular pool of PKC isozymes. However, in most investigations only TPA, as the most potent tumor-promoting phorbol ester, has been used. Inspite of observations that other phorbol esters exert more specific biological effects in vivo, relatively few studies have been reported so far on their interaction with individual PKC isozymes in vitro or in vivo. In vivo interaction of different phorbol esters with PKC involves penetration of the phorbol ester molecule into the inner layer of the cellular membrane and binding to the regulatory domain of PKC followed by redistribution of the PKC pool from the cytosolic to the membrane bound fraction. It is thought that PKC redistribution ("translocation") is followed by an activation step and phosphorylation of substrate(s). Tigliane (TPA, PdBu, DOPP, DOPPA and Sap A) and daphnane (Thy A and Rx) diterpenoids of the phorbol ester group, were investigated for their ability to interact with purified recombinant protein kinase C (PKC) isozymes. Representative compounds of distinct biological activity were chosen in an attempt to establish a correlation between their in vivo effects and their ability to interact with individual PKC isozymes. Utilising PKC isozymes α, β1, β2, ỿ, δ, ε, and ζ purified from a baculovirus/Sf9 insect cell expression system and a phosphatidylserine / Triton X-100 mixed micellar system as an in vitro cell membrane model, binding and activation of PKC isozymes by seven different phorbol esters was studied. Binding affinity and activation potency of individual compounds were found to correlate well with high tumor promoting activity of TPA and PdBu on one side and with the non-promoting action of DOPPA and Rx. However, the non-promoters DOPP and Sap A and a second stage tumor promoter Thy A were effective agonists of PKC isozymes. To study the ability of some PEs to induce association of PKC isozymes with cellular membranes (i.e. "translocation"), a membrane fraction obtained from HL-60 cells was used, in order to approach in vivo conditions. Although the ability of the investigated PEs to induce "translocation" of PKC isozymes corresponded to their ability to induce PKC activation, the ability of micromolar Ca2+ concentrations to induce membrane association of n-PKCs, ε and δ, was not in agreement with our activation results and current theory of Ca2+ independency of the n-PKC isozymes. These results suggested that specific biological effects of different phorbol esters could not solely be explained through differences in their interaction with PKC isozymes in vitro. It is possible that an intracellular component, absent in an artificial system, is responsible for modulation of phorbol ester effects in vivo. Additionally a daphnane diterpene and a second stage tumor promoter mezerein, was isolated from previously uninvestigated Daphne blagayana, a plant indegenous to the Balkan. For the first time, detailed one and two dimensional NMR (1H, 13C, COSY and NOESY) experiments were conducted to confirm the previously determined structure of mezerein. Computer assisted molecular modelling and structure analysis enabled determination of molecular minimum free energy and interatomic distances of the pharmacophore's functional groups. These values were similar to those obtained for a highly potent tumor promoter TPA. As an activator of individual PKC isozymes in vitro, mezerein appeared to be different from TPA. Mezerein was relatively less potent (when compared with TPA) as an activator of the novel PKC isozymes δ and ε. This suggested that differences in biological activity of mezerein and TPA could be, in part, due to differences in their ability to activate the PKC isozymes δ and ε

The influence of the radiative non-symmetric ion-atom collisions on the stellar atmospheres in VUV region

The aim of this work is to draw attention to the processes of radiative charge exchange in non-symmetric ion-atom collisions as a factor of influence on the opacity of stellar atmospheres in VUV region. For that purpose calculations of the spectral absorption coefficients for several ion-atom systems, namely: He + H$^{+}$ and H + X$^{+}$, where X = Na and Li have been performed. On chosen examples it has been established that the examined processes generate rather wide molecular absorption bands in the VUV region, which should be taken into account for the interpretation of data obtained from laboratory measurements or astrophysical observations. In this paper the potential significance is discussed of the considered radiative processes for DB white dwarfs and solar atmospheres, as well as for the atmospheres of the so-called lithium stars

The flux ratio of the [OIII] 5007,4959 lines in AGN: Comparison with theoretical calculations

By taking into account relativistic corrections to the magnetic dipole operator, the theoretical [OIII] 5006.843/4958.511 line intensity ratio of 2.98 is obtained. In order to check this new value using AGN spectra we present the measurements of the flux ratio of the [OIII] 4959,5007 emission lines for a sample of 62 AGN, obtained from the Sloan Digital Sky Survey (SDSS) Database and from published observations. We select only high signal-to-noise ratio spectra for which the line shapes of the [OIII] 4959,5007 lines are the same. We obtained an averaged flux ratio of 2.993 +/- 0.014, which is in a good agreement with the theoretical one.Comment: Accepted for publication in the MNRA

The ion-atom absorption processes as one of the factors of the influence on the sunspot opacity

As a continuation of the previous investigations of the symmetric and strongly non-symmetric ion-atom absorption processes in the far UV region within the models of the quiet Sun photosphere, these processes are studied here within a model of the sunspot. Here we mean the absorption processes in the H$(1s)$+H$^{+}$ and H$(1s)+X^{+}$ collisions and the processes of the photo-dissociation of the H$_{2}^{+}$ and H$X^{+}$ molecular ions, where $X$ is one of the metal atoms: $X=$Na, Ca, Mg, Si and Al. Obtained results show that the influence of the considered ion-atom absorption processes on the opacity of sunspots in the considered spectral region (110 nm $\lesssim \lambda \lesssim$ 230 nm) is not less and in some parts even larger than the influence of the referent electron-atom processes. In such a way, it is shown that the considered ion-atom absorption processes should be included \emph{ab initio} in the corresponding models of sunspots of solar-type and near solar-type stars. Apart of that, the spectral characteristics of the considered non-symmetric ion-atom absorption processes (including here the case $X$ = Li), which can be used in some further applications, have been determined and presented within this work.Comment: Accepted in Monthly Notices of the Royal Astronomical Societ

Excitation and deexcitation processes in atom-Rydberg atom collisions in helium-rich white dwarf atmospheres

We aim to show the importance of non-elastic excitation and deexcitation processes in $\textrm{He}^{*}(n)+ \textrm{He}(1s^{2})$ collisions with the principal quantum number $n \ge 3$ for helium-rich white dwarf atmospheres. We compare the efficiencies of these processes with those of the known non-elastic electron-$\textrm{He}^{*}(n)$ atom processes in the atmospheres of some DB white dwarfs. We show that in significant parts of the considered atmospheres, which contain weakly ionized layers (the ionization degree $\lesssim 10^{-3}$), the influence of the studied atom-Rydberg atom processes on excited helium atom populations is dominant or at least comparable to the influence of the concurrent electron-$\textrm{He}^{*}(n)$-atom processes.Comment: Astronomy & Astrophysics, Accepted: 14 February 201

Ion-atom radiative processes in the solar atmosphere: quiet Sun and sunspots

In the previous works the significance of the symmetric and non-symmetric ion-atom absorption processes in far UV and EUV regions within a model of the quiet Sun atmosphere, has been studied. The considered processes were the processes of the photo-dissociation of the molecular ions H$_{2}^{+}$ and H$X^{+}$ and absorption processes in H+H$^{+}$ and H$+X^{+}$ collisions, where $X$ denotes the metal atom. As the continuation of the previous investigation, these processes are considered also within the corresponding sunspot model. In this work the non-symmetric ion-atom absorption processes are considered with $X=$ Mg, Si, etc. It was analyzed the significance of such processes in far UV and EUV regions in comparison with the concurrent absorption processes, especially with the processes of the photo-ionization of the metal atoms (Na, Mg, Ca, etc.) which were not included in the consideration in the case of the quiet Sun atmosphere. From our analysis it follows that the non-symmetric ion-atom absorption processes considered here, are significant not only for quiet Sun modeling but also for sunspots and should be included {\it ab initio} in both cases.Comment: accepted in Advances in Space Researc

On the influence of Stark broadening on Si I lines in stellar atmospheres

We study the influence of Stark broadening and stratification effects on Si\i lines in the rapidly oscillating (roAp) star 10 Aql, where the Si\i 6142.48 \AA and 6155.13 \AA lines are asymmetrical and shifted. First we have calculated Stark broadening parameters using the semiclassical perturbation method for three Si\i lines: 5950.2 \AA, 6142.48 \AA and 6155.13 \AA. We revised the synthetic sp$ calculation code taking into account both Stark width and shift for these lines. From the comparison of our calculations with the observations we found that Stark broadening + the stratification effect can explain asymmetry of the Si\i 6142.48 \AA and 6155.13 \AA lines in the atmospere of roAp star 10 Aql.Comment: Accepted to A&

Stark Broadening of in III Lines in Astrophysical and Laboratory Plasma

Besides the need of Stark broadening parameters for a number of problems in physics, and plasma technology, in hot star atmospheres the conditions exist where Stark widths are comparable and even larger than the thermal Doppler widths. Using the semiclassical perturbation method we investigated here the influence of collisions with charged particles for In III spectral lines. We determined a number of Stark broadening parameters important for the investigation of plasmas in the atmospheres of A-type stars and white dwarfs. Also, we have compared the obtained results with existing experimental data. The results will be included in the STARK-B database, the Virtual Atomic and Molecular Data Center and the Serbian Virtual Observatory