Vadim V. Shmanai
National Academy of Sciences of Belarus
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Featured researches published by Vadim V. Shmanai.
Free Radical Biology and Medicine | 2012
Shauna Hill; Connor R. Lamberson; Libin Xu; Randy To; Hui S. Tsui; Vadim V. Shmanai; Andrei V. Bekish; Agape M. Awad; Beth N. Marbois; Charles R. Cantor; Ned A. Porter; Catherine F. Clarke; Mikhail S. Shchepinov
Polyunsaturated fatty acids (PUFAs) undergo autoxidation and generate reactive carbonyl compounds that are toxic to cells and associated with apoptotic cell death, age-related neurodegenerative diseases, and atherosclerosis. PUFA autoxidation is initiated by the abstraction of bis-allylic hydrogen atoms. Replacement of the bis-allylic hydrogen atoms with deuterium atoms (termed site-specific isotope-reinforcement) arrests PUFA autoxidation due to the isotope effect. Kinetic competition experiments show that the kinetic isotope effect for the propagation rate constant of Lin autoxidation compared to that of 11,11-D(2)-Lin is 12.8 ± 0.6. We investigate the effects of different isotope-reinforced PUFAs and natural PUFAs on the viability of coenzyme Q-deficient Saccharomyces cerevisiae coq mutants and wild-type yeast subjected to copper stress. Cells treated with a C11-BODIPY fluorescent probe to monitor lipid oxidation products show that lipid peroxidation precedes the loss of viability due to H-PUFA toxicity. We show that replacement of just one bis-allylic hydrogen atom with deuterium is sufficient to arrest lipid autoxidation. In contrast, PUFAs reinforced with two deuterium atoms at mono-allylic sites remain susceptible to autoxidation. Surprisingly, yeast treated with a mixture of approximately 20%:80% isotope-reinforced D-PUFA:natural H-PUFA are protected from lipid autoxidation-mediated cell killing. The findings reported here show that inclusion of only a small fraction of PUFAs deuterated at the bis-allylic sites is sufficient to profoundly inhibit the chain reaction of nondeuterated PUFAs in yeast.
Free Radical Biology and Medicine | 2015
Alexander Y. Andreyev; Hui S. Tsui; Ginger L. Milne; Vadim V. Shmanai; Andrei V. Bekish; Maksim A. Fomich; Minhhan N. Pham; Yvonne Nong; Anne N. Murphy; Catherine F. Clarke; Mikhail S. Shchepinov
Polyunsaturated fatty acid (PUFA) peroxidation is initiated by hydrogen atom abstraction at bis-allylic sites and sets in motion a chain reaction that generates multiple toxic products associated with numerous disorders. Replacement of bis-allylic hydrogens of PUFAs with deuterium atoms (D-PUFAs), termed site-specific isotope reinforcement, inhibits PUFA peroxidation and confers cell protection against oxidative stress. We demonstrate that structurally diverse deuterated PUFAs similarly protect against oxidative stress-induced injury in both yeast and mammalian (myoblast H9C2) cells. Cell protection occurs specifically at the lipid peroxidation step, as the formation of isoprostanes, immediate products of lipid peroxidation, is drastically suppressed by D-PUFAs. Mitochondrial bioenergetics function is a likely downstream target of oxidative stress and a subject of protection by D-PUFAs. Pretreatment of cells with D-PUFAs is shown to prevent inhibition of maximal uncoupler-stimulated respiration as well as increased mitochondrial uncoupling, in response to oxidative stress induced by agents with diverse mechanisms of action, including t-butylhydroperoxide, ethacrynic acid, or ferrous iron. Analysis of structure-activity relationships of PUFAs harboring deuterium at distinct sites suggests that there may be a mechanism supplementary to the kinetic isotope effect of deuterium abstraction off the bis-allylic sites that accounts for the protection rendered by deuteration of PUFAs. Paradoxically, PUFAs with partially deuterated bis-allylic positions that retain vulnerable hydrogen atoms (e.g., monodeuterated 11-D1-Lin) protect in a manner similar to that of PUFAs with completely deuterated bis-allylic positions (e.g., 11,11-D2-Lin). Moreover, inclusion of just a fraction of deuterated PUFAs (20-50%) in the total pool of PUFAs preserves mitochondrial respiratory function and confers cell protection. The results indicate that the therapeutic potential of D-PUFAs may derive from the preservation of mitochondrial function.
Analytical and Bioanalytical Chemistry | 2012
Dmitry Y. Ryazantsev; Dmitry A. Tsybulsky; Igor A. Prokhorenko; Maksim V. Kvach; Yury V. Martynenko; Pavel M. Philipchenko; Vadim V. Shmanai; Vladimir A. Korshun; S. K. Zavriev
AbstractA typical TaqMan™ real-time PCR probe contains a 5′-fluorescent dye and a 3′-quencher. In the course of the amplification, the probe is degraded starting from the 5′-end, thus releasing fluorescent dye. Some fluorophores (including fluorescein) are known to be prone to self-quenching when located near each other. This work is aimed at studying dye–dye and dye–quencher interactions in multiply modified DNA probes. Twenty-one fluorogenic probes containing one and two fluoresceins (FAM), or a FAM–JOE pair, and one or two BHQ1 quenchers were synthesized using non-nucleoside reagents and “click chemistry” post-modification on solid phase and in solution. The probes were tested in real-time PCR using an ~300-bp-long natural DNA fragment as a template. The structural prerequisites for lowering the probe background fluorescence and increasing the end-plateau fluorescence intensity were evaluated and discussed. FigureFluorogenic TaqMan probes with various modifications for real-time PCR
Food Chemistry | 2015
Sergey Tumanov; Yuri Zubenko; Marc Greven; David R. Greenwood; Vadim V. Shmanai; Silas G. Villas-Bôas
This study presents a comprehensive lipidome analysis of Sauvignon blanc grape juice by combining GC-MS based fatty acid profiling with shotgun lipidomics strategy. We observed that despite grape juice being a water based matrix it contains a diverse range of lipid species, including common saturated and unsaturated free and intact fatty acids as well as odd-numbered and hydroxy fatty acids. Based on GC-MS quantitative data, we found that the total lipid content of grape juice could be as high as 2.80 g/L. The majority of lipids were present in the form of complex lipids with relatively small amount of free fatty acids (<15%). Therefore we concluded that the lipidome should be considered an important component of grape juice with the potential to impact on fermentation processes as well as on the sensorial properties of fermented products. This work serves as a hypothesis generating tool, the results of which justify follow-up studies to explore the influence of the grape juice lipidome and lipid metabolism in yeast on the aroma profile of wine.
Organic Letters | 2014
Maksim A. Fomich; Maksim V. Kvach; Maksim J. Navakouski; Christoph Weise; Alexander V. Baranovsky; Vladimir A. Korshun; Vadim V. Shmanai
Azide and phosphoramidite functions were found to be compatible within one molecule and stable for months in solution kept frozen at -20 °C. An azide-carrying phosphoramidite was used for direct introduction of multiple azide modifications into synthetic oligonucleotides. A series of azide-containing oligonucleotides were modified further using click reactions with alkynes.
Biochemical Pharmacology | 2014
Geo Semini; Annette Hildmann; Andreas Klein; Lothar Lucka; Margarete Schön; Michael P. Schön; Vadim V. Shmanai; Kerstin Danker
In cutaneous inflammatory diseases, such as psoriasis, atopic dermatitis and allergic contact dermatitis, skin-infiltrating T lymphocytes and dendritic cells modulate keratinocyte function via the secretion of pro-inflammatory cytokines. Keratinocytes then produce mediators that recruit and activate immune cells and amplify the inflammatory response. These pathophysiological tissue changes are caused by altered gene expression and the proliferation and maturation of dermal and epidermal cells. We recently demonstrated that the glycosidated phospholipid Ino-C2-PAF down-regulates a plethora of gene products associated with innate and acquired immune responses and inflammation in the HaCaT keratinocyte cell line. To further evaluate the influence of Ino-C2-PAF we established an in vitro 2D-model of epidermal inflammation. The induction of inflammation and the impact of Ino-C2-PAF were assessed in this system using a genome-wide microarray analysis. In addition, the expression of selected genes was validated using qRT-PCR and flow cytometry. Treatment of the keratinocytes with a mix of proinflammatory cytokines resulted in transcriptional effects on a variety of genes involved in cutaneous inflammation and immunity, while additional treatment with Ino-C2-PAF counteracted the induction of many of these genes. Remarkably, Ino-C2-PAF suppressed the expression of a group of targets that are implicated in antigen processing and presentation, including MHC molecules. Thus, it is conceivable that Ino-C2-PAF possess therapeutic potential for inflammatory skin disorders, such as psoriasis and allergic contact dermatitis.
Bioorganic & Medicinal Chemistry Letters | 2011
Nikolay B. Pestov; Irina A. Okkelman; Vadim V. Shmanai; Alaksiej L. Hurski; Amato J. Giaccia; Mikhail S. Shchepinov
Lysyl oxidase (LOX) is implicated in several extracellular matrix related disorders, including fibrosis and cancer. Methods of inhibition of LOX in vivo include antibodies, copper sequestration and toxic small molecules such as β-aminopropionitrile. Here, we propose a novel approach to modulation of LOX activity based on the kinetic isotope effect (KIE). We show that 6,6-d(2)-lysine is oxidised by LOX at substantially lower rate, with apparent deuterium effect on V(max)/K(m) as high as 4.35 ± 0.22. Lys is an essential nutrient, so dietary ingestion of D(2)Lys and its incorporation via normal Lys turnover suggests new approaches to mitigating LOX-associated pathologies.
Nature Chemical Biology | 2018
Michael M. Gaschler; Alexander A. Andia; Hengrui Liu; Joleen M. Csuka; Brisa Hurlocker; Christopher A. Vaiana; Daniel W. Heindel; Dylan S. Zuckerman; Pieter H. Bos; Eduard Reznik; Ling F. Ye; Yulia Y. Tyurina; Annie J. Lin; Mikhail S. Shchepinov; Amy Y. Chan; Eveliz Peguero-Pereira; Maksim A. Fomich; Jacob. D. Daniels; Andrei V. Bekish; Vadim V. Shmanai; Valerian E. Kagan; Lara K. Mahal; K. A. Woerpel; Brent R. Stockwell
AbstractFerroptosis is a non-apoptotic form of regulated cell death caused by the failure of the glutathione-dependent lipid-peroxide-scavenging network. FINO2 is an endoperoxide-containing 1,2-dioxolane that can initiate ferroptosis selectively in engineered cancer cells. We investigated the mechanism and structural features necessary for ferroptosis initiation by FINO2. We found that FINO2 requires both an endoperoxide moiety and a nearby hydroxyl head group to initiate ferroptosis. In contrast to previously described ferroptosis inducers, FINO2 does not inhibit system xc– or directly target the reducing enzyme GPX4, as do erastin and RSL3, respectively, nor does it deplete GPX4 protein, as does FIN56. Instead, FINO2 both indirectly inhibits GPX4 enzymatic function and directly oxidizes iron, ultimately causing widespread lipid peroxidation. These findings suggest that endoperoxides such as FINO2 can initiate a multipronged mechanism of ferroptosis.FINO2 is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid peroxidation.
Metabolomics | 2016
Sergey Tumanov; Yuri Zubenko; Vladimir Obolonkin; David R. Greenwood; Vadim V. Shmanai; Silas G. Villas-Bôas
IntroductionTechnological advances in the area of analytical chemistry and the development of state-of-the-art analytical instrumentation have allowed for a shift in the focus from a previously strict targeted approach towards the approach adopted in metabolomics, the essence of which is non-targeted providing an unbiased analysis of metabolites in biological samples. Metabolite profiling methods have served their purpose in providing descriptive information about biological systems through qualitative and relative semi-quantitative data. However, quantitative characterization of a system cannot be fully accomplished without using absolute metabolite concentrations, an area which is lacking in most current metabolomics platforms.ObjectivesThe objective of this work was to develop a calibration-curve free method for quantitation of amino and non-amino organic acids in biological samples.MethodsWe developed a novel calibration curve-free GC–MS method based on isotope-coded derivatization for absolute non-targeted quantification of polar metabolites. A new R-based package MetabQ was created for automated data processing of GC–MS data files performing data extraction and calculation of absolute metabolite values. The new method requires metabolite response factors which should be calculated only once for each equipment, and was validated for metabolite quantification of different biological matrices.ResultsThe method showed high reproducibility and accuracy, and does not require the use of calibration curves using standards to be analyzed in parallel with every sample batch. However, there is a small group of metabolites where their quantification required additional steps of correction due to their chemical instability. The introduced R package significantly increased the throughput in the data analysis process, extensively reducing the time required to perform the task manually.ConclusionOur novel approach gives the potential to identify and quantify hundreds of metabolites, far exceeding the capabilities of any absolute quantitative targeted metabolite analysis, limited only by the size of the mass spectral library.
Langmuir | 2016
Aleksandra Fedosyuk; Aliaksandra Radchanka; Artsiom Antanovich; Anatol Prudnikau; Maksim V. Kvach; Vadim V. Shmanai; Mikhail Artemyev
We present a method for the determination of the average number of polymer molecules on the surface of A(II)B(VI) luminescent core-shell nanocrystals (CdSe/ZnS, ZnSe/ZnS quantum dots, and CdS/ZnS nanorods) encapsulated with amphiphilic polymer. Poly(maleic anhydride-alt-1-tetradecene) (PMAT) was quantitatively labeled with amino-derivative of fluorescein and the average amount of PMAT molecules per single nanocrystal was determined using optical absorption of the dye in the visible spectral range. The average amount of PMAT molecules grows linearly with the surface area of all studied nanocrystals. However, the surface density of the monomer units increases nonlinearly with the surface area, because of the increased competition between PMAT molecules for Zn-hexanethiol surface binding sites. The average value of zeta potential (ζ = -35 mV) was found to be independent of the size, shape, and chemical composition of nanocrystals at fixed buffer parameters (carbonate-bicarbonate buffer, pH 9.5 and 5 mM ionic strength). This finding is expected to be useful for the determination of the surface density of remaining carboxyl groups in PMAT-encapsulated nanocrystals.