Oxidative stress and its effect on cell functional activity in Alzheimer’s disease

The review summarizes literature data on the importance of oxidative stress as one of the pathogenetic mechanisms in Alzheimer’s disease. Special attention is paid to the main specific and nonspecific ways of reactive oxygen species (ROS) generation in the course of the disease development. Generated ROS influence functional activity of cells, particularly, apoptosis and the mitotic cycle. Phosphorylation/dephosphorylation processes associated with intense phosphorylation of tau protein and mitosis-specific proteins play the nodal regulatory role in the cell. Alzheimer’s disease is accompanied by impairments of the regulatory functions of peptidyl-prolyl isomerases, particularly, Pin1 involved in maintaining a balanced state of phosphorylation/dephosphorylation processes. Taking into consideration the multifactorial impairment of the cell cycle control, this process should be considered from the viewpoint of the general state of metabolic processes, and oxidative stress has one of the key positions in aging.     

Vacuoles of Mesophyll Cells as a Transient Reservoir for Assimilates

We studied the efflux of radioactive photosynthetic products from the central vacuole into the cytosol of protoplasts isolated from the mesophyll tissue of the sugar beet (Beta vulgaris L.) after their darkening and subsequent cessation of photosynthesis. Among the products accumulated in the vacuole were the ¹⁴C-labelled sugars malate and alanine, small amounts of citric, glutamic, and aspartic acids, and some other amino acids. During the initial 20–30 min of darkness, there was no substantial utilization of photoassimilates accumulated in the vacuole during the preceding light period. An efflux of assimilates occurred later, after 30–40 min of darkness. A decrease in the vacuolar ¹⁴C-sucrose occurred not only due to its exit into the cytosol but also because of its conversion into ¹⁴C-monosaccharides by the vacuolar invertase. In fact, this decrease in the sucrose content correlated well with the accumulation of monosaccharides. Immediately after photosynthesis ceased, the chloroplastic ¹⁴C-starch was utilized for the maintenance of cytoplasmic metabolism. After 30-min darkness, the content of starch in the chloroplasts decreased by several times. We believe that the vacuoles of sugar-beet mesophyll cells are transient reservoirs for assimilates and the products of their conversion (glucose and fructose), which can rapidly leave the vacuole to maintain homeostasis in the cytosol under varying environmental conditions.     

Role of nitric oxide in tumor growth

This review article will analyze the role of nitric oxide in antiblastomous organism resistance, in particular some mechanisms of NO-mediated apoptosis in different cells and NO involvement in etiological mechanisms as well as tumor growth promotion. The possible mechanisms of nitric oxide dual effect are discussed. The data about NO as a mediator in different methods of cancer treatment are given. In conclusion, we have determined some principles of application of NO-modulating agents in cancer therapy.     

The role of oxygen in the regulation of the metabolism of aerotolerant spirochetes,a major component of <Emphasis Type="Italic">“Thiodendron”</Emphasis> bacterial sulfur mats

Two spirochete strains isolated earlier from Thiodendron bacterial sulfur mats grew better under microaerobic (0.3–0.5 mg O₂/l) than under anaerobic conditions. The microaerobic growth of these strains was accompanied by a twofold increase in the cell yield and the efficiency of glucose utilization, despite the fact that an additional amount of ATP (and, hence, glucose) was spent in this case for the synthesis of exopolysaccharides. Glucose metabolism under microaerobic conditions gave rise to more oxidized products (acetate and carbon dioxide) than under anaerobic conditions (formate, ethanol, pyruvate, and hydrogen). The paper considers two putative mechanisms implemented by aerotolerant spirochetes: adaptive (the use of a more efficient pathway of glucose catabolism) and protective (an enhanced synthesis of exopolysaccharides and the reduction of hydrogen peroxide by the reduced sulfur compounds thiosulfate and sulfide, yielding elemental sulfur). The formation of Thiodendron bacterial sulfur mats in saltwater environments is also discussed.Translated from Mikrobiologiya, Vol. 73, No. 6, 2004, pp. 725–733.Original Russian Text Copyright © 2004 by Dubinina, Grabovich, Chernyshova.     

The functional role of reduced inorganic sulfur compounds in the metabolism of the microaerophilic bacterium Spirillum winogradskii

Oxidation of reduced sulfur compounds by microaerophilic sulfur bacterium Spirillum winogradskii was found to occur only concomitantly with consumption of an organic substrate and was not linked to their utilization as electron donors in energy metabolism. No enzymes of dissimilatory sulfur metabolism were found in the cells of the sulfur bacterium oxidizing thiosulfate to tetrathionate; oxidation of thiosulfate and sulfide was caused by their reaction with reactive oxygen species (ROS), mostly H2O2 produced in the course of aerobic growth. Decreased lytic effect of ROS in the presence of thiosulfate resulted in a twofold increase in the cell yield under aerobic conditions and more efficient substrate utilization. The latter effect was caused by decreased expense of energy for the biosynthesis of oxygen-protecting polysaccharides. The stimulatory effect of thiosulfate on the growth processes was due to the activation of a number of TCA cycle enzymes producing the intermediates for constructive metabolism, especially of the NADP-dependent malic enzyme. As a result of thiosulfate-induced synthesis of SH-containing cell components, the integral antioxidative activity increased 1.5-fold.     

Mitomycin C-induced mutagenesis

The mutagenic effect of mitomycin C (MC) has been shown in the S phase of Crepic capillaris cells. The repair ability of MC-induced DNA lesions proves exceedingly high, due to post-replicative and excision repair processes. In the experiments with MC-pretreatment of Crepic capillaris cells, nonmutagenic concentration of 1 microgram/ml provides inducible repair system--"adaptive response", which considerably decreases the levels of mutagenesis induced by MC at concentrations of 10, 20 and 40 micrograms/ml. Under adaptive response, the action of methyltransferase is possible.     

Infection of procaryotic and eucaryotic microorganisms withMetallogenium

To elucidate the biological characteristics ofMetallogenium, a study was undertaken into the effect of infection of such organisms unable to oxidize manganese as fungi, yeasts, and bacteria with an ultrafiltrate of this organism on the subsequent behavior of the resulting binary cultures. The infection of microorganism cultures is accompanied by (a) acquisition by the binary cultures of a persistent capacity to oxidize manganese, (b) evolution of the characteristic structures ofMetallogenium (c) inhibition of the growth of the inoculated cultures; the inhibition manifests itself by fungi losing their capacity for spore formation and pigmentation, the upsetting of cell division processes, and lysis of the cells of the infected cultures all the way to death. When a heated ultrafiltrate ofMetallogenium was used to infect microorganism cultures, no signs of infection were detected.Metallogenium may be hosted by an extremely broad range of microorganisms that are in no way allied to one another. The experimental results suggest thatMetallogenium is an organism capable of parasitizing lower eucaryotic and procaryotic microorganisms. Analysis of 134 strains of fungi isolated from freshwater bodies is indicative of possible parasitism ofMetallogenium on microorganisms in their natural habitats.     

Detection and analysis of sulfur metabolism genes in Sphaerotilus natans subsp. sulfidivorans representatives

The lithotrophic capacity of the betaproteobacteria Sphaerotilus natans subsp. sulfidivorans was confirmed at the genetic level: functional genes of sulfur metabolism were detected (aprBA, soxB, and sqr, coding for adenylyl phosphosulfate reductase, thiosulfate-cleaving enzyme, and sulfide:quinone oxidoreductase, respectively), and the expression of aprA and soxB genes was demonstrated. An evolutionary scenario for soxB genes in Sphaerotilus representatives is suggested based on comparative analysis of codon occurrence frequency, DNA base composition (G+C content), and topology of phylogenetic trees. The ancestor bacterium of the Sphaerotilus-Leptothrix group was capable of lithotrophic growth in the presence of reduced sulfur compounds. However, in the course of further evolution, the sulfur metabolism genes, including the soxB gene, were lost by some Sphaerotilus strains. As a result, the lithotrophic Sphaerotilus-Leptothrix group split into two phylogenetic lineages: lithotrophic and organotrophic ones.