V A Vakhitov

Ufa Scientific Center of the Russian Academy of Science, Oufa, Bashkortostan, Russia

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Publications (52)22.69 Total impact

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    ABSTRACT: Background Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aß25¿35-induced toxicity in PC12 cells and revealed the underlying mechanisms.ResultsThe neuroprotective effect of noopept (added to the medium at 10 ¿M concentration, 72 hours before ¿ß25¿35) was studied on ¿ß25¿35-induced injury (5 ¿M for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by ¿ß25¿35 were evaluated.Following the exposure of PC12 cells to ¿ß25¿35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by ¿ß25¿35.Conclusions Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aß through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway. Moreover, neuroprotective properties of noopept likely include its ability to decrease tau phosphorylation and to restore the altered morphology of PC12 cells. Therefore, this nootropic dipeptide is able to positively affect not only common pathogenic pathways but also disease-specific mechanisms underlying Aß-related pathology.
    Journal of Biomedical Science 08/2014; 21(1):74. DOI:10.1186/s12929-014-0074-2 · 2.74 Impact Factor
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    ABSTRACT: Test systems for monitoring activities and the search for substances activating or inhibiting transcription factors as biological targets have been designed on the basis of luciferase constructs containing binding sites for transcription factors CREB, NFAT, NF-κB, p53, STAT1, GAS, VDR, HSF1, and HIF1α. An assessment of the functional activity of reporter constructs has been carried out using their transient transfection into HEK293 cells followed by treatment with specific inducers. The functional activity of all reporter constructs was observed based on the increased luciferase expression. In order to evaluate the efficiency of the suggested test systems, aspirin was used. Incubation of cells transfected with the above-mentioned constructs treated with aspirin was accompanied by the suppression of NF-κB, HIF1α, GAS, VDR, and HSF binding activity. The findings revealed for NF-κB, NFAT, and STAT1 confirm the published data concerning the mechanisms of aspirin action. The detected effects of this drug on the HIF1α, GAS, VDR, and CREB activity have been demonstrated for the first time.
    Applied Biochemistry and Microbiology 03/2014; 50(2). DOI:10.1134/S000368381402015X · 0.66 Impact Factor
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    ABSTRACT: Transgenic tobacco plants expressing the AINTEGUMENTA gene of rape under control of the 35S promoter and the promoter of dahlia mosaic virus were obtained. The transgenic plants were characterized by increase in the length of the leaves, flower sizes, stem height, and weight of seeds; at the same time, the degree of increase was greater in the case of use of the dahlia mosaic virus promoter as a regulator of transcription. Ectopic expression of the AINTEGUMENTA gene promoted prolongation of leaf growth, while sizes of epidermal cells of the leaves remained unchanged.
    Russian Journal of Developmental Biology 03/2013; 44(2). DOI:10.1134/S1062360413020070 · 0.22 Impact Factor
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    ABSTRACT: Elevation of intracellular Ca²⁺ in T-lymphocytes as a consequence of T cell antigen receptor activation triggers transcriptional programs resulting in effector cytokine secretion and immune response coordination. Increase of Ca²⁺ concentration in T-lymphocytes follows both the Ins(1,4,5)P(3)-dependent release from an intracellular store and subsequent influx from extracellular milieu. Flow cytometry and the fluorescent dye Fluo-4AM have been used to demonstrate that noncompetitive NMDA receptor antagonist (+)-MK801 inhibits Ca²⁺ influx in T cells induced by thapsigargin. Combination of thapsigargin and (+)-MK801 with following incubation does not affect Ca²⁺ mobilization from intracellular stores, while decreased Ca²⁺ entry was observed. Overall data indicate that the ion channel blocker (+)-MK801 is able to inhibit the Ca²⁺ influx and confirm our suggestion about involvement of NMDA receptor in the store-operated Ca²⁺ entry mechanisms in human T-lymphocytes. To identify the signal transduction pathways associated with NMDA receptors in mitogen-stimulated T-lymphocytes, the cells were incubated with (+)-MK801, then activity of key phosphorylated protein kinases of MAP-activated (pERK1/2, pSAPK/JNK, p-p38), Ca²⁺-dependent (pCaMKII), PI3/Akt-dependent (pGSK-3β), and PKC-activated (pPKCθ) pathways were detected. The data we obtained demonstrate that (+)-MK801 treatment leads to more prominent decrease in Ras-activated protein kinases pERK1/2 and Rac-activated proteins p-p38 and pSAPK/JNK, as compared to DAG-dependent pPKCθ and Ca²⁺-dependent pCaMKII. These results show that NMDA receptors are mainly involved in regulation of Ras/Rac-dependent signaling in T-lymphocytes.
    Biochemistry (Moscow) 11/2011; 76(11):1220-6. DOI:10.1134/S0006297911110034 · 1.35 Impact Factor
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    ABSTRACT: Under action of growth-stimulating concentrations of bioregulator stifun on wheat plants, an increase of functional activity Under action of growth-stimulating concentrations of bioregulator stifun on wheat plants, an increase of functional activity of nucleoli of meristematic cells; contents of lectin (wheat germ agglutinin); and activity of proteinases, tripsin inhibitors, of nucleoli of meristematic cells; contents of lectin (wheat germ agglutinin); and activity of proteinases, tripsin inhibitors, and ATPase activity was established. The pool of free amino acids was increased under bioregulator use. Levels of methionine, and ATPase activity was established. The pool of free amino acids was increased under bioregulator use. Levels of methionine, phenylalanine, cysteine, lysine, leucine and tyrosine were increased. It is likely that stifun could activate protein biosynthesis phenylalanine, cysteine, lysine, leucine and tyrosine were increased. It is likely that stifun could activate protein biosynthesis in wheat plants. in wheat plants.
    Applied Biochemistry and Microbiology 11/2011; 47(6):621-626. DOI:10.1134/S0003683811060123 · 0.66 Impact Factor
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    ABSTRACT: Under action of growth-stimulating concentrations of bioregulator stifun on wheat plants, an increase of functional activity of nucleoli of meristematic cells; contents of lectin (wheat germ agglutinin); and activity of proteinases, tripsin inhibitors, and ATPase activity was established. The pool of free amino acids was increased under bioregulator use. Levels of methionine, phenylalanine, cysteine, lysine, and tyrosine were increased. It is likely that stifun could activate protein biosynthesis in wheat plants.
    Prikladnaia biokhimiia i mikrobiologiia 01/2011; 47(6):679-84.
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    ABSTRACT: New approaches to the detection of impaired nucleotides based on the allele specific ligation of a "C probe" followed by rolling circle amplification have been developed. The detection of amplification products was realized by using enzymatic and deoxyribozyme digestion of fluorescently-labeled DNA-RNA-DNA chimeric oligonucleotide structures in cycling probe technology (CPT) in real-time mode.
    Bioorganicheskaia khimiia 09/2009; 35(5):665-73. DOI:10.1134/S1068162009050100
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    ABSTRACT: Plant responses to cadmium, whose accumulation may cause various disturbances in metabolic processes, can be represented as a multicomponent integrative response model (in particular, as a gan-shaped response) [1]. In view of this, it is reasonable to use a complex approach to analyzing plant responses to cadmium, which may include studies of plant adaptation, cadmium accumulation, and detoxication. The goal of this work was to study plant responses to cadmium and its accumulation in plants. The study included characterizing the resistance of plants by changes in the proportion of linear sizes and weight; determination of the degree of hydration, phytohormone balance, and the content of free amino acids; establishing the mechanisms of occurrence of chromosome rearrangements on the basis of analysis of the distribution of chromosome aberrations in cells and the aberration index under exposure to cadmium; and assessment of the retaining ability and barrier function of roots during cadmium entry into sprouts. The study was performed with the cibol ( Allium fistulosum L.) cultivars Gribovskii and Russkii zimnii; the spring wheat ( Triticum aestivum L.) cultivars Zhnitsa, Irmenka, and Omskaya-35; the maize ( Zea mays L.) cultivar Zhemchug; and the rice ( Oryza sativa L.) cultivar Rapan. Seeds were sterilized with 70% ethanol. Seedlings were grown in Petri dishes on filter paper wetter with water in a constant-temperature cabinet at 24‐27 ° C. Aligned 48-h-old seedlings were incubated with cadmium acetate for 18, 36, and 54 h (cibol); 24, 48, 72, 96, and 120 h (maize and wheat); and 1, 24, and 48 h (rice). In addition, wheat seeds were allowed to germinate at 24 ° C for 24 h, placed on cork rafts with 4-mm holes, and grown in vessels filled with cadmium acetate for 14 days. During the entire experiment, solutions were aerated and their volume was maintained constant by adding distilled water. Distilled water was used as a control. The resistance index was determined by the ratio between the plant weight in the presence of cadmium and in the control [2]. We studied the effect of cadmium on the intensity of division of apical meristematic cells, the nucleolus characteristics, the level of chromosome aberrations in root meristematic cells (by metaphase and anaphase methods), the content of phytohormones (abscisic acid (ABA), indolylacetic acid (IAA), and cytokinins by enzyme immunoassay), as well as the content of free amino acids by ionexchange chromatography. The content of cadmium was determined by the Experiments were performed in quadruplicate and repeated at least five times. The statistical significance of differences between variants was estimated by Student’s t test. In the presence of cadmium at concentrations of 100, 10, and 1 mg/l, the resistance index of wheat was 0.75, 0.98, and 0.92 (Zhnitsa); 0.69, 1.03, and 1.05 (Omskaya-35); and 0.73, 0.88, and 1.05 (Irmenka), respectively. At these concentrations, the sprout/root ratio obtained after determination of linear sizes was 0.70, 1.31, 0.72, and 0.70 (Zhnitsa); 0.51, 1.06, 0.51, and 0.61 (Omskaya-35); and 0.63, 1.41, 0.70, and 0.60 (Irmenka), respectively. In the presence of 100 mg/l cadmium, the degree of hydration of plants significantly decreased: by 45% (Zhnitsa), 41% (Irmenka), and 41% (Omskaya-35). At concentrations of 10 and 1 mg/l, cadmium had no effect on the degree of hydration. The potential of wheat resistance to cadmium determined at early developmental stages in the Barsukova medium varied from very low (0.21) to very high (1.2) [2]. Thus, we did not reveal significant genotypic differences in plant responses to cadmium at the concentrations used.
    Doklady Biological Sciences 06/2009; 426:274-7. DOI:10.1134/S0012496609030247
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    ABSTRACT: The physiological activity of the plant growth regulator Epin-extra is investigated under conditions of sodium chloride salinity, cadmium stress, and low temperature. Epin-extra lessens the negative effect of stress factors on growth of spring wheat, Welsh onion, and cabbage: it reduces the level of cadmium-induced chromosome aberrations and concentration of this metal in plants exposed to a cadmium acetate solution. An increase of the level of expression of the cabbage cold shock protein gene (CSP5) under the effect of the bioregulator is established by the real-time PCR method with the use of interprimer fluorescence resonance energy transfer.
    Russian Agricultural Sciences 06/2009; 35(3):163-165. DOI:10.3103/S1068367409030094
  • Doklady Biochemistry and Biophysics 04/2008; 419(1):53-5. DOI:10.1134/S1607672908020014 · 0.37 Impact Factor
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    ABSTRACT: The effect of stifun on wheat, Welsh onion, and corn plants under the effect of cadmium is investigated. The protective effect of this bioregulator manifested itself in preventing inhibition of growth, stabilizing mitotic phases, and reducing the level of chromosomal aberrations. The results of histochemical investigations permit the assumption that growth regulators can reduce the uptake of cadmium ions into plant tissues.
    Russian Agricultural Sciences 08/2007; 33(4):233-235. DOI:10.3103/S1068367407040064
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    ABSTRACT: The effect of benzyladenine (BA) on the activation of rRNA gene transcription was studied in wheat (Triticum aestivum and T. urartu) as related to the phenomenon of nucleolar dominance and the changes in the extent of methylation of the intergenic spacers in the subgenome A. The method of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to analyze the fragments of rDNA promoter regions amplified with the primers designed to recognize the sites of DNA isolated from BA-treated seedlings of diploid T. urartu and hexaploid T. aestivum and desaminated with metabisulfite. The subsequent genomic bisulfite sequencing of the amplification products was used to evaluate the level of methylation/demethylation of the particular cytosine residues. BA diminished methylation of cytosine residues in rDNA promoter regions to the level, which was different in two wheat species; these data presume that the transcriptional activities of rRNA genes in various wheat subgenomes depend on the extent of their methylation.
    Russian Journal of Plant Physiology 01/2007; 54(2):207-214. DOI:10.1134/S1021443707020082 · 0.76 Impact Factor
  • Doklady Biochemistry and Biophysics 12/2006; 411:349-50. DOI:10.1134/S160767290606007X · 0.37 Impact Factor
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    ABSTRACT: Without Abstract
    Doklady Biochemistry and Biophysics 12/2006; 411:327-30. DOI:10.1134/S1607672906060019 · 0.37 Impact Factor
  • Doklady Biochemistry and Biophysics 03/2005; 401:150-3. DOI:10.1007/s10628-005-0057-z · 0.37 Impact Factor
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    ABSTRACT: The Atlas Rat cDNA Expression Array (BD Biosciences, United States) has been used to analyze changes in the expression of 588 genes in rat brain cells in response to a single administration of Ladasten, a 2-aminoadamantane derivative that has psychostimulating and anxiolytic effects. The analysis of hybridization on macroarrays, confirmed by the results of real-time quantitative RT-PCR, has demonstrated that Ladasten alters the expression of 12 genes in the rat brain. The GAT3 and CARBH genes are presumed to be pharmacologically important targets of Ladasten. The changes in their activity explain the mechanisms of the anxiolytic and mood-stabilizing effects of the drug. Ladasten has been shown to induce the genes whose products are involved in various signal pathways (APC, Rb, PKCIP, and PMCA), as well as the genes of cytoskeletal proteins (Tub1 and actin), synaptic proteins (SynIA&IB and PLP), and enzymes (Gapdh and NSE). The proteins encoded by these genes are presumably involved in compensatory and/or neuroplastic adaptation to the effects of Ladasten.
    Molecular Biology 02/2005; 39(2):244-252. DOI:10.1007/s11008-005-0035-7 · 0.74 Impact Factor
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    ABSTRACT: We have used the Rat Atlas cDNA Array ("BD Bioscience") to assess changes in mRNA expression of 588 genes in rat brain after acute treatment of 2-aminoadamantane compound--Ladasten. Drug exhibits the psychostimulating and anxyolitic actions. The analysis of results of hybridization on macrochips and their corroboration by quantitative real-time RT-PCR has allowed to reveal 12 genes, expression of which changes in response to ladasten in rat brain cells. The GAT3 and CARBH genes should be considered as primary pharmacologically significant targets and the changes of their functional conditions allows to explain the distinct mechanisms of anxyolitic properties of the drug. It was shown that Ladasten induced genes are involved in the different signalling pathways (APC, Rb, PKCIP, PMCA), genes encoding the cytosceletal proteins (Tubal, actin), synaptic proteins (Syn IA&IB, PLP) and metabolism enzymes (Gapdh, NSE). It is possible to assume, that proteins, encoded by the given genes participate in the compensatory and/or neuroplastic adaptation to biochemical effects of Ladasten.
    Molekuliarnaia biologiia 01/2005; 39(2):276-85.
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    ABSTRACT: A significant heterogeneity between bacteria Rhizobium galegae bv. officinalis and R. galegae bv. orientalis forming the nitrogen-fixing symbiosis with Galega officinalis and G. orientalis, respectively, and not forming any single cross-inoculation group, was found by means of RAPD and RFEL methods. The high level of sequence similiraty between lectins of these plants indicates at their close relationship. However the sequences of lectin sugar binding peptides (SBP) of G. orientalis (TYCNPGWDPRDR) and G. officinalis (TFYNEEWDLVIKDEH) were highly diverged. Amino acids of SBP which are involved in linkage of Ca2+ and Mn2+ ions responsible for stabilization of spatial structure of carbohydrate-binding "pocket", keep their position in peptide. It suggests that lectins participate in Rhizobium-legume symbiosis and that carbohydrate-binding site plays a key role in this process.
    Molekuliarnaia biologiia 01/2005; 39(1):103-11.
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    ABSTRACT: RAPD and RFEL analyses revealed appreciable genetic heterogeneity of Rhizobium galegae bv. officinalis and R. galegae bv. orientalis, which are nitrogen-fixing symbiosis partners of Galega officinalis and G. orientalis, respectively, and do not form a single cross-inoculation group. Comparison of nucleotide and amino acid sequences for their lectins revealed relatively high general homology, testifying again to their close phylogenetic relationships. Yet the lectin region of the carbohydrate-binding peptide (CBP) proved to differ considerably, being TYCNPGWDPRDR in G. orientalis and TFYNEEWDLVIKDEH in G. officinalis. Conserved positions in the CBP were observed for amino acid residues involved in binding Ca2+ and Mn2+ and stabilizing the spatial structure of the carbohydrate-binding pocket. These findings confirm the role in Rhizobium— legume symbiosis for lectins and especially for their carbohydrate-binding domains.
    Molecular Biology 12/2004; 39(1):90-97. DOI:10.1007/s11008-005-0013-0 · 0.74 Impact Factor
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    ABSTRACT: Some stages of low-temperature signal transduction causing appropriate cold stress response in plants are considered. The effects of Ca2+ chelators, Ca2+ channel blockers, and protein kinase inhibitors on protoplasts and plants of cabbage suggest that the initial stages of cold signal transduction are the change in membrane fluidity followed by the activation of calcium channels and elevation of Ca2+ influx into the cytoplasm. Increased concentration of Ca2+ in cytoplasm activates calcium-dependent protein kinase most likely participating in induction of transcription factors necessary for the expression of cold-regulated genes, in particular csp5. The protein kinase inhibitors staurosporine and wortmannin insignificantly repress the expression of csp5.
    Biochemistry (Moscow) 06/2004; 69(5):575-9. DOI:10.1023/B:BIRY.0000029857.05522.d5 · 1.35 Impact Factor

Publication Stats

201 Citations
22.69 Total Impact Points

Institutions

  • 1997–2014
    • Ufa Scientific Center of the Russian Academy of Science
      • Institute of Organic Chemistry
      Oufa, Bashkortostan, Russia
  • 2005
    • Russian Academy of Sciences
      • Institute of Biochemistry and Genetics
      Moskva, Moscow, Russia
  • 2001
    • Institute of Biology, Ufa Research Centre RAS
      Oufa, Bashkortostan, Russia