Avicin D: A Protein Reactive Plant Isoprenoid Dephosphorylates Stat 3 by Regulating Both Kinase and Phosphatase Activities

Avicins, a class of electrophilic triterpenoids with pro-apoptotic, anti-inflammatory and antioxidant properties, have been shown to induce redox-dependant post-translational modification of cysteine residues to regulate protein function. Based on (a) the cross-talk that occurs between redox and phosphorylation processes, and (b) the role of Stat3 in the process of apoptosis and carcinogenesis, we chose to study the effects of avicins on the processes of phosphorylation/dephosphorylation in Stat3. Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3. The expression of Stat3-regulated proteins such as c-myc, cyclin D1, Bcl2, survivin and VEGF were reduced in response to avicin treatment. Underlying avicin-induced dephosphorylation of Stat3 was dephosphorylation of JAKs, as well as activation of protein phosphatase-1. Downregulation of both Stat3 activity and expression of Stat 3-controlled pro-survival proteins, contributes to the induction of apoptosis in avicin treated tumor cells. Based on the role of Stat3 in inflammation and wounding, and the in vivo inhibition of VEGF by avicins in a mouse skin carcinogenesis model, it is likely that avicin-induced inhibition of Stat3 activity results in the suppression of the pro-inflammatory and pro-oxidant stromal environment of tumors. Activation of PP-1, which also acts as a cellular economizer, combined with the redox regulation by avicins, can aid in redirecting metabolism from growth promoting anabolic to energy sparing pathways

A possible restriction of ferro- and ferricyanide oxidoreductase activities of rat liver mitochondria by the outer membrane.

In this work, various ferro-ferricyanide oxidoreductase activities of rat liver mitochondria were studied to find conditions under which the outer membrane might restrict the flux of these highly charged non-biological anions. When the isotonic low ionic strength medium was supplemented with 25mM KCl, a several-fold increase in the succinate-ferricyanide reductase activity of mitochondria and in the rate of external NADH oxidation in the presence of ferrocyanide was observed. Mitochondrial respiration with 5mM ferrocyanide was almost completely inhibited after consumption of 3.8-18.5% of the dissolved oxygen, depending on the medium and the presence of 2,4-dinitrophenol. These and other experimental data together with mathematical modeling of the redox-state equilibrium suggest that the measured activities might be restricted by two factors: first, the permeability of the outer mitochondrial membrane and second, a strong influence of the ionic strength of incubation media on the intermembrane space redox reactions

Effect of paracetamol on the microsomal oxidation, oxidative phosphorylation and liver mitochondria swelling in rats of various ages

The effect of hepatotoxic dose of paracetamol (800 mg per kg, intraperitoneally, once a day during two days) on the system of microsomal oxidation, respiration, oxidative phosphorylation and high amplitude swelling of liver mitochondria was studied on 1-, 4- and 30-months old Wistar male rats. It has been shown, that paracetamol injection leads to the decrease of content of cytochrome P-450, to disorders of the function of monooxygenase system (the aminopyrine-N-demethylase and aniline hydroxylase activities were diminished), mitochondria macrostructure (the mitochondria high amplitude swelling time was decreased) and function (the respiratory control was decreased). These alterations have been observed to manifest to more extent in the liver of young rats as compared with old ones

Experimental and field research: Vertical structure of the field of current velocities in the northwest part of the Black Sea based on the LADCP data for May 2004

The profiles of absolute current velocity obtained by using a lowered acoustic doppler current profiler (LADCP) are presented. In the course of the BSERP-3 expedition, the measurements were carried out in the regions of the Rim Current, anticyclonic eddy, and northwest shelf. In the core of the Rim Current, a unidirectional motion of waters is traced in layers below the main pycnocline down to depths greater than 500 m. Its characteristic velocity can be as high as 0.08 m/sec. It is shown that the direct action of the eddy is detected in the shelf region at distances larger than 20 km from the outer edge of the shelf in the zone bounded by an isobath of 100 m. The formation of multilayer vertical structures in the field of current velocities is revealed in the region of interaction of the anticyclonic eddy with irregularities of the bottom on the side of the shelf. A two-layer structure of currents with specific features in the layer of formed seasonal pycnocline is observed in the region of the shelf down to an isobath of 100 m. The profiles of the moduli of vertical shears of currents averaged over the casts ensemble are presented for the abyssal and shelf parts of the sea. It is shown that the shears induced by the geostrophic currents and wave processes in the region of the main pycnocline are comparable. Below the pycnocline, the shears are mainly determined by the wave processes. © 2008 Springer Science+Business Media, Inc