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Pustylnyak V.O.,Novosibirsk State University | Lisachev P.D.,Russian Academy of Sciences | Shtark M.B.,Institute of Molecular Biology and Biophysics | Epstein O.I.,OOO nPF mATERIA MEDICA HOLDING
Brain Research

In the present study we investigated the regulation of S100B expression during tetanization-induced hippocampal long term potentiation, one of the best characterized forms of synaptic plasticity. Tetanization resulted in time-dependent change in S100B gene expression and protein content in hippocampal CA1 area. We analyzed the promoter region of the rat S100B gene and identified response elements for the tumor suppressor p53. ChIP assay revealed that p53 could bind to putative p53-binding sites of the S100B promoter. The time-dependent recruitment of p53 to its putative binding sites in the S100B gene promoter paralleled the time-course change of S100B mRNA and protein levels. Thus, these results strongly support the view that S100B gene may be a target of p53. Moreover, we demonstrated that the increase of S100B protein content was accompanied with the decrease of p53 protein content, and it seems that the decrease is regulated on post-translational level. Thus, our results may help to understand the physiological function of the p53-S100B-p53 loop in the process of synaptic plasticity. © 2011 Elsevier B.V. All rights reserved. Source

Lyakhovich A.,Masaryk University | Lyakhovich A.,St Annes University Hospital Brno | Lyakhovich A.,Institute of Molecular Biology and Biophysics | Graifer D.,Novosibirsk State University | And 3 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer

Given the key role of mitochondria in various cellular events, it is not surprising that mitochondrial dysfunction (MDF) is seen in many pathological conditions, in particular cancer. The mechanisms defining MDF are not clearly understood and may involve genetic defects, misbalance of reactive oxygen species (ROS), impaired autophagy (mitophagy), acquired mutations in mitochondrial or nuclear DNA and inability of cells to cope with the consequences. The importance of MDF arises from its detection in the syndromes with defective DNA damage response (DDR) and cancer predisposition. Here, we will focus on the dual role of these syndromes in cancer predisposition and MDF with specific emphasis on impaired autophagy. © 2016 Elsevier B.V. Source

Kazantseva Y.A.,Institute of Molecular Biology and Biophysics | Pustylnyak Y.A.,Novosibirsk State University | Pustylnyak V.O.,Novosibirsk State University
Biochemistry (Moscow)

Activation of the constitutive androstane receptor (CAR) in hepatocytes occurs as a body adaptation in response to a number of external influences, and its functional activity is primarily related to induction of enzymes detoxifying xenobiotics. However, special attention was recently given to CAR due to the fact that its key role becomes unveiled in various physiological and pathophysiological processes occurring in the liver: gluconeogenesis, metabolism of fatty acids and bilirubin, hormonal regulation, proliferation of hepatocytes, and hepatocarcinogenesis. Here we review the main pathways and mechanisms that elevate hepatocyte proliferative activity related to CAR and whose disturbance may be a pivotal factor in hepatocarcinogenesis. © 2016, Pleiades Publishing, Ltd. Source

Suhovskih A.V.,Karolinska Institutet | Suhovskih A.V.,Institute of Molecular Biology and Biophysics | Kashuba V.I.,Karolinska Institutet | Kashuba V.I.,NASU Institute of Molecular Biology and Genetics | And 3 more authors.
Cell Adhesion and Migration

Microenvironment and stromal fibroblasts are able to inhibit tumor cell proliferation both through secreted signaling molecules and direct cell-cell interactions but molecular mechanisms of these effects remain unclear. In this study, we investigated a role of cell-cell contact-related molecules (protein ECM components, proteoglycans (PGs) and junction-related molecules) in intercellular communications between the human TERT immortalized fibroblasts (BjTERT fibroblasts) and normal (PNT2) or cancer (LNCaP, PC3, DU145) prostate epithelial cells. It was shown that BjTERT-PNT2 cell coculture resulted in significant decrease of both BjTERT and PNT2 proliferation rates and reorganization of transcriptional activity of cell-cell contact-related genes in both cell types. Immunocytochemical staining revealed redistribution of DCN and LUM in PNT2 cells and significant increase of SDC1 at the intercellular contact zones between BjTERT and PNT2 cells, suggesting active involvement of the PGs in cell-cell contacts and contact inhibition of cell proliferation. Unlike to PNT2 cells, PC3 cells did not respond to BjTERT in terms of PGs expression, moderately increased transcriptional activity of junctions-related genes (especially tight junction) and failed to establish PC3-BjTERT contacts. At the same time, PC3 cells significantly down-regulated junctions-related genes (especially focal adhesions and adherens junctions) in BjTERT fibroblasts resulting in visible preference for homotypic PC3-PC3 over heterotypic PC3-BjTERT contacts and autonomous growth of PC3 clones. Taken together, the results demonstrate that an instructing role of fibroblasts to normal prostate epithelial cells is revoked by cancer cells through deregulation of proteoglycans and junction molecules expression and overall disorganization of fibroblast-cancer cell communication. ©2016 Taylor & Francis Source

Iyevleva A.G.,St Petersburg Pediatric Medical Academy | Suspitsin E.N.,St Petersburg Pediatric Medical Academy | Kroeze K.,Leiden University | Gorodnova T.V.,St Petersburg Pediatric Medical Academy | And 8 more authors.
Cancer Letters

A few founder BRCA1 mutations (5382insC, 4154delA, 185delAG) account for up to 15% of high-risk (young-onset or familial or bilateral) breast cancer (BC) cases in Russia. The impact of non-founder BRCA1 mutations in this country is less studied; in particular, there are no reports analyzing gross rearrangements of this gene in the Russian patient series. We selected for the study 95 founder mutation negative high-risk BC cases. Combination of high-resolution melting (HRM) and sequencing revealed six presumably BC-associated alleles (2080delA, 4808C > G, 5214C > T, 5236G > A, 5460G > T, 5622C > T) and one variant of an unknown significance (4885G > A). The pathogenic role of the 5236G > A mutation leading to G1706E substitution was further confirmed by the loss of heterozygosity analysis of the corresponding tumor tissue. Multiplex ligation-dependent probe amplification (MLPA) revealed two additional BRCA1 heterozygotes, which carried BRCA1 deletions involving exons 1-2 and 3-7, respectively. Based on the results of this investigation and the review of prior Russian studies, three BRCA1 mutations (2080delA, 3819del5, 3875del4) were considered with respect to their possible founder effect and tested in the additional series of 210 high-risk BC patients; two BRCA heterozygotes (2080delA and 3819del5) were revealed. We conclude that the non-founder mutations constitute the minority of BRCA1 defects in Russia. © 2010 Elsevier Ireland Ltd. Source

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