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Markozashvili D.,University Paris - Sud | Markozashvili D.,Lia 1066 Laboratoire Franco Russe Of Recherche En Oncologie | Pichugin A.,University Paris - Sud | Pichugin A.,Lia 1066 Laboratoire Franco Russe Of Recherche En Oncologie | And 12 more authors.
Gene | Year: 2016

Mantle cell lymphoma (MCL) is a rare lymphoma caused by the t(11:14) juxtaposing the cyclin D1 (CCND1) locus on chromosome 11 and the immunoglobulin heavy chain (IgH) locus on chromosome 14. Several new treatments are proposed for MCL, including histone deacetylase inhibitors (HDACi). We have studied gene expression and chromatin organization in the translocated 11q13 locus in MCL cells as compared to lymphoblastoid cell lines as well as the effect of HDACi abexinostat on chromatin organization and gene expression in the 11q13 locus. We have identified a cluster of genes overexpressed in the translocation region on chromosome 11 in MCL cells. Abexinostat provokes a genome-wide disaggregation of heterochromatin. The genes upregulated after the t(11;14) translocation react to the HDACi treatment by increasing their expression, but their gene promoters do not show significant alterations in H3K9Ac and H3K9me2 levels in abexinostat-treated cells. © 2016 Elsevier B.V.


Bou Saada Y.,University Paris - Sud | Dib C.,University Paris - Sud | Dmitriev P.,University Paris - Sud | Hamade A.,Lebanese University | And 5 more authors.
Histochemistry and Cell Biology | Year: 2016

Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy linked to a deletion of a subset of D4Z4 macrosatellite repeats accompanied by a chromatin relaxation of the D4Z4 array on chromosome 4q. In vitro, FSHD primary myoblasts show altered expression of oxidative-related genes and are more susceptible to oxidative stress. Double homeobox 4 (DUX4) gene, encoded within each D4Z4 unit, is normally transcriptionally silenced but is found aberrantly expressed in skeletal muscles of FSHD patients. Its expression leads to a deregulation of DUX4 target genes including those implicated in redox balance. Here, we assessed DNA repair efficiency of oxidative DNA damage in FSHD myoblasts and DUX4-transfected myoblasts. We have shown that the DNA repair activity is altered neither in FSHD myoblasts nor in immortalized human myoblasts transiently expressing DUX4. DNA damage caused by moderate doses of an oxidant is efficiently repaired while FSHD myoblasts exposed for 24 h to high levels of oxidative stress accumulated more DNA damage than normal myoblasts, suggesting that FSHD myoblasts remain more vulnerable to oxidative stress at high doses of oxidants. © 2016 Springer-Verlag Berlin Heidelberg


Zakhidov S.T.,Moscow State University | Pavlyuchenkova S.M.,Moscow State University | Marshak T.L.,Koltzov Institute of Developmental Biology | Rudoy V.M.,RAS Frumkin Institute of Physical Chemistry and Electrochemistry | And 6 more authors.
Biology Bulletin | Year: 2012

The response of the mouse male germ cells exposed to gold nanoparticles (~2.5 nm) was studied. Our investigation demonstrates that treatment with Au nanoparticles for four days does not impair the architecture of the spermatogenic epithelium. Cytogenetic evaluation using micronucleus assay showed that gold nanoparticles can affect the chromosomes of early primary spermatocytes. However, gold nanoparticles did not induce chromosome abnormalities in spermatogonial stem cells. Further, the cauda epididymal sperm was isolated on the 14th day after treatment and was incubated in SDS solution (Na dodecyl sulphate) and then in a solution containing DTT (dithiothreitol) to induce nuclear chromatin decondensation. Observations showed that after four days of treatment of spermiogenic (postmeiotic) cells with gold nanoparticles the decondensation process had no differences from the control. On the contrary, in the experiment with the same cells and period of fixation but with a single exposure to gold nanoparticles, the number of mature gametes with totally decondensed nuclei reached 100% as opposed to 44% in the controls. © 2012 Pleiades Publishing, Ltd.


Zakhidov S.T.,Moscow State University | Pavlyuchenkova S.M.,Moscow State University | Samoylov A.V.,Koltzov Institute of Developmental Biology | Mudzhiri N.M.,Moscow State University | And 6 more authors.
Biology Bulletin | Year: 2013

The response of ejaculated bovine spermatozoa to gold nanoparticles was studied by the standard method of nuclear chromatin decondensation in vitro. After the treatment of semen samples with a hydrosol containing gold nanoparticles with an average diameter of ∼3.0 nm and a concentration of 1 × 1015 particles/mL, the ability of sperm nuclei to decondense in the presence of sodium dodecyl sulfate (SDS) and dithiothreitol (DTT) dramatically changed compared to the control. The frequencies of gametes with nondecondensed ("intact"), partially decondensed, and completely decondensed nuclei correlated as 40: 32: 28% and 0: 36: 64% in the experiment and the control, respectively. Moreover, the appearance of a sufficiently large number of gametes with destructed and almost completely destroyed nuclei was noticed in the spermatozoa treated with gold nanoparticles. This article suggests the putative mechanisms of action of ultrasmall gold nanoparticles on the structural and functional integrity of the deoxyribonucleoprotein (DNP) complex of mature male gametes. © 2013 Pleiades Publishing, Inc.


Kulibin A.Yu.,Koltzov Institute of Developmental Biology | Malolina E.A.,RAS D. I. Ivanovsky Institute of Virology
Tsitologiya | Year: 2013

Sertoli cells (SCs) isolated from adult C57Bl/6 mice were characterized under four different cell culture conditions: standard conditions (34 °C, 21 % O2 - 34-21), high-temperature conditions (37 °C, 21 % O 2 - 37-21), hypoxic conditions (34 °C, 5 % O2 - 34-5), and combination of these conditions (37 °C, 5 % O2 - 37-5). Proliferation and viability were promoted when SCs were grown under hypoxia: 28.5 and 24.6 % of SCs were BrdU-positive at the peak of proliferation, 92.7 and 92.7 % of SCs were viable after 15 days in culture at 34-5 and 37-5, respectively, versus 20.2 and 88.9 % at 34-21, respectively. In SCs grown under high-temperature conditions proliferation was slightly increased, but viability was decreased: 23.1 % of SCs were BrdU-positive, and only 74.9 % of SCs were viable at 37-21. At the same time cultivation of SCs at 37 °C promoted their dedifferentiation: after 15 days in culture 98.8 and 98.6 % of cells at 37-5 and 37-21, respectively, expressed a marker of immature SCs - cytokeratin-18, compared to 26.5 % at 34-5 and 6.6 % at 34-21. Expression of Wt1, a transcription factor controlling cell-cell junction formation and germ cell development, disappeared in most cells after 3 days in culture under all culture conditions. However, SCs forming colonies restored Wt1 expression at day 15 in culture under high-temperature conditions: 59.1 and 29.5 % of SCs were Wt1-positive at 37-21 and 37-5, respectively, versus 11.1 and 3.6 % at 34-21 and 34-5, respectively. Cultured SCs expressed other SC markers (vimentin, clusterin, Gata-4) under all culture conditions. Our results show that cultured SCs may be useful for reproductive biology and regenerative medicine.


Ivashkin E.,Koltzov Institute of Developmental Biology | Adameyko I.,Karolinska Institutet
EvoDevo | Year: 2013

The neural crest represents a highly multipotent population of embryonic stem cells found only in vertebrate embryos. Acquisition of the neural crest during the evolution of vertebrates was a great advantage, providing Chordata animals with the first cellular cartilage, bone, dentition, advanced nervous system and other innovations. Today not much is known about the evolutionary origin of neural crest cells. Here we propose a novel scenario in which the neural crest originates from neuroectodermal progenitors of the pigmented ocelli in Amphioxus-like animals. We suggest that because of changes in photoreception needs, these multipotent progenitors of photoreceptors gained the ability to migrate outside of the central nervous system and subsequently started to give rise to neural, glial and pigmented progeny at the periphery. © 2013 Ivashkin and Adameyko.; licensee BioMed Central Ltd.


Senchenko V.N.,RAS Engelhardt Institute of Molecular Biology | Kisseljova N.P.,Nn Blokhin Russian Cancer Research Center | Ivanova T.A.,Nn Blokhin Russian Cancer Research Center | Dmitriev A.A.,RAS Engelhardt Institute of Molecular Biology | And 8 more authors.
Epigenetics : official journal of the DNA Methylation Society | Year: 2013

Genetic and epigenetic alterations in cervical carcinomas were investigated using NotI-microarrays containing 180 cloned sequences flanking all NotI-sites associated with genes on chromosome 3. In total, 48 paired normal/tumor DNA samples, specifically enriched in NotI-sites, were hybridized to NotI-microarrays. Thirty genes, including tumor suppressors or candidates (for example, VHL, RBSP3/CTDSPL, ITGA9, LRRC3B, ALDH1L1, EPHB1) and genes previously unknown as cancer-associated (ABHD5, C3orf77, PRL32, LOC285375, FGD5 and others), showed methylation/deletion in 21-44% of tumors. The genes were more frequently altered in squamous cell carcinomas (SCC) than in adenocarcinomas (ADC, p<0.01). A set of seven potential markers (LRRN1, PRICKLE2, VHL, BHLHE40, RBSP3, CGGBP1 and SOX14) is promising for discrimination of ADC and SCC. Alterations of more than 20 genes simultaneously were revealed in 23% of SCC. Bisulfite sequencing analysis confirmed methylation as a frequent event in SCC. High down-regulation frequency was shown for RBSP3, ITGA9, VILL, APRG1/C3orf35 and RASSF1 (isoform A) genes (3p21.3 locus) in SCC. Both frequency and extent of RASSF1A and RBSP3 mRNA level decrease were more pronounced in tumors with lymph node metastases compared with non-metastatic ones (p ≤ 0.05). We confirmed by bisulfite sequencing that RASSF1 promoter methylation was a rare event in SCC and, for the first time, demonstrated RASSF1A down-regulation at both the mRNA and protein levels without promoter methylation in tumors of this histological type. Thus, our data revealed novel tumor suppressor candidates located on chromosome 3 and a frequent loss of epigenetic stability of 3p21.3 locus in combination with down-regulation of genes in cervical cancer.


Brodsky V.Y.,Koltzov Institute of Developmental Biology | Rapoport S.I.,Moscow Medical Academy | Dubovaya T.K.,Moscow State University | Zvezdina N.D.,Koltzov Institute of Developmental Biology | And 2 more authors.
Russian Journal of Developmental Biology | Year: 2010

Melatonin injected intraperitoneally into rat synchronizes the ultradian rhythm of protein synthesis after 100 min in primary hepatocyte cultures isolated from this rat, which are studied after 1 or 2 days. The effective synchronization concentrations of melatonin-0.01-0.02 μg per kg of rat weight-are three orders lower than melatonin doses used in clinical practice in human treatment. © 2010 Pleiades Publishing, Ltd.


Luchnik A.N.,Koltzov Institute of Developmental Biology
Gene Regulation and Systems Biology | Year: 2014

Regulation of transcription in eukaryotes is considered in the light of recent findings demonstrating the presence of negative and positive superhelical tension in chromatin. This tension induces conformational transitions in DNA duplex. Particularly, the transition into A-form renders DNA accessible and waylaying for initiation of transcription producing RNA molecules long known to belong to the A-conformation. Competition between conformational transitions in various DNA sequences for the energy of elastic spring opens a possibility for understanding of fine tuning of transcription at a distance. © the authors, publisher and licensee Libertas Academica Limited.


Novikova Yu.P.,Koltzov Institute of Developmental Biology | Gancharova O.S.,Moscow State University | Eichler O.V.,Moscow State University | Philippov P.P.,Moscow State University | Grigoryan E.N.,Koltzov Institute of Developmental Biology
Biochemistry (Moscow) | Year: 2014

The human retina is constantly affected by light of varying intensity, this being especially true for photoreceptor cells and retinal pigment epithelium. Traditionally, photoinduced damages of the retina are induced by visible light of high intensity in albino rats using the LIRD (light-induced retinal degeneration) model. This model allows study of pathological processes in the retina and the search for retinoprotectors preventing retinal photodamage. In addition, the etiology and mechanisms of retina damage in the LIRD model have much in common with the mechanisms of the development of age-related retinal disorders, in particular, with age-related macular degeneration (AMD). We have studied preventive and therapeutic effects of Visomitin eye drops (based on the mitochondria-targeted antioxidant SkQ1) on albino rat retinas damaged by bright light. In the first series of experiments, rats receiving Visomitin for two weeks prior to illumination demonstrated significantly less expressed atrophic and degenerative changes in the retina compared to animals receiving similar drops with no SkQ1. In the second series, the illuminated rats were treated for two weeks with Visomitin or similar drops without SkQ1. The damaged retinas of the experimental animals were repaired much more effectively than those of the control animals. Therefore, we conclude that Visomitin SkQ1-containing eye drops have pronounced preventive and therapeutic effects on the photodamaged retina and might be recommended as a photoprotector and a pharmaceutical preparation for the treatment of AMD in combination with conventional medicines. © Pleiades Publishing, Ltd., 2014.

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