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Biomedical subjects

A V Ivanova

Publications and source records attributed to A V Ivanova.

At least 19 recordsLinked to original sources
PubMed2006

Hypoxic repression of STAT1 and its downstream genes by a pVHL/HIF-1 target DEC1/STRA13.

DEC1/STRA13 is a bHLH type transcriptional regulator involved with immune regulation, hypoxia response and carcinogenesis. We recently demonstrated that STRA13 interacts with STAT3 in the transcriptional activation of STAT-dependent promoters. Here, we pursue STRA13 involvement in the JAK/STAT pathway by studying its role in STAT1 expression. First, we showed that VHL deficiency or HIF-1 activation resulted in the repression of endogenous STAT1 mediated by STRA13. We then characterized the STAT1 proximal promoter to assess its response to STRA13 by transient coexpression in a luciferase reporter assay. Using sequential truncation and site-directed mutagenesis of the STAT1 promoter with STRA13 deletion constructs, we showed that the STRA13 C-terminal trans-activation domain, which is known to bind HDAC1, mostly determines the repressive activity. Involvement of HDAC activity in STAT1 regulation was validated by TSA inhibition and chromatin immunoprecipitation (ChIP) assay. Thus, we demonstrate that STRA13-mediated repression of STAT1 transcription utilizes an HDAC1-dependent mechanism. Furthermore, we show that targets of unphosphorylated STAT1, such as antigen presenting genes and CASP1, are also repressed by hypoxia possibly through the same STRA13-mediated mechanism. Thus, the newly discovered link between HIF-1 and STAT1 reveals a previously unknown role of STRA13 in hypoxia and carcinogenesis.

Amino Acid Motifs↗
PubMed2005

Association, mutual stabilization, and transcriptional activity of the STRA13 and MSP58 proteins.

STRA13 is a hypoxia-inducible bHLH transcription factor implicated in the pVHL/HIF, TGF-beta, and Jak/STAT pathways. To further characterize the STRA13 protein-interacting network and mechanisms of STRA13-dependent transcription, we utilized yeast two-hybrid screening. Here we report on STRA13 interaction with the cell cycle-associated transcription factor MSP58. We demonstrated that the basic domain of STRA13 and the FHA domain of MSP58 are essential for this association. We performed phospho-peptide mapping of both MSP58 and STRA13 and showed that their association was modulated by the STRA13 phosphorylation status. STRA13/MSP58 complex formation protected both proteins from the proteasome-mediated degradation, extending their half-lives considerably. STRA13 and MSP58 synergistically co-operated in the STRA13 promoter-driven transcription repression. Both proteins were co-localized in the nucleus and showed transcript accumulation during the S phase of the cell cycle. Thus, we characterize a novel STRA13-associated transcription repression complex and provide a link between cell cycle regulation and STRA13 activity.

Alternative Splicing↗
PubMed2004

STRA13 interacts with STAT3 and modulates transcription of STAT3-dependent targets.

STRA13 is a pVHL-dependent bHLH transcription factor up-regulated on the mRNA level in multiple cancer cell lines and implicated recently in the regulation of immune cell homeostasis and autoimmunity. In searching for STRA13-interacting proteins with oncogenic potential by the yeast two-hybrid screening, we identified STAT3 beta as a STRA13-binding partner. We showed that STRA13 binds predominantly to phosphorylated (active) STAT3 alpha and beta isoforms via its HLH and C-terminal regions. We also found that STRA13 was able to activate transcription from STAT-dependent cis-elements. Expression of endogenous STRA13 was shown to be cytokine-inducible, consistent with STRA13 involvement in STAT-dependent transcription regulation. We demonstrated that the STAT3-regulated promoter of the pro-apoptotic Fas gene was activated upon STRA13 over-expression and that co-expression of STRA13 with STAT3 beta or STAT3 alpha modulated the transcriptional outcome. Forced expression of STRA13 induced apoptosis, in agreement with the STRA13 activation effect on the Fas promoter. Simultaneous expression of STRA13 and STAT3 beta resulted in alleviation of the STRA13 pro-apoptotic effect. Thus, for the first time, we identify STRA13 as a STAT3 partner and provide a consistent line of evidence for STRA13 involvement into regulation of apoptosis via the STAT pathways.

Amino Acid Sequence↗
PubMed2004

Preventive and therapeutic effect of complex antioxidant preparation in rats with burn trauma.

The production of blood radicals and activity of superoxide dismutase in erythrocytes increased in rats with contact burn trauma (20%). In animals with burn trauma antioxidant activity of the plasma was much lower, while myeloperoxidase content in the lung tissue and epidermis was higher than in control rats. The complex of antioxidants (Immudzhen) inhibited radical generation at the peak of inflammation (day 4), increased antioxidant activity of the plasma, and normalized myeloperoxidase content in the lung tissue.

Animals↗
PubMed2004

Wound-healing effect of papaya-based preparation in experimental thermal trauma.

Treatment with the phytopreparation from papaya accelerated wound healing and reduced the severity of local inflammation in rats with burn wounds. The effect of this phytopreparation can be related to an increase in the effectiveness of intracellular bacterial killing by tissue phagocytes due to the inhibition of bacterial catalase. Antioxidant activity of the preparation decreases the risk of oxidative damage to tissues.

Animals↗
PubMed2002

Differential display analysis of gene expression in yeast.

RNA differential display (DD) is a powerful and straightforward method that employs random reverse-transcription polymerase chain reaction amplification of mRNA species with electrophoresis for comparative analysis of two or more transcriptomes. The small yeast genome represents a convenient model for studying basic functions of the eukaryotic genome and simultaneously provides valuable information towards further refinement of this technique. Several examples discussed below illustrate how DD coupled with classical yeast genetic approaches may be used for studying transcriptionally regulated genetic systems.

Blotting, Northern↗
PubMed2002

Mapping of two dominant sites of VP35 of Marburg virus.

Five types of anti-VP35 monoclonal antibodies (MAbs), four immune sera against Marburg virus (MBGV), and 11 overlapping recombinant VP35 fragments were used to map the epitopes for VP35 of MBGV. The purified full-size recombinant VP35 was highly immunogenic and retained the B-cell epitopes that were identical to those of the viral VP35. Two major sites on VP35 and a set of truncated VP35 fragments were found by use of an enzyme immunoassay and immunoblot. Site I was located in a region between amino acids 1 and 174 of the VP35 sequence, and only polyclonal antibodies (PAbs) against MBGV recognized epitopes at this site. Site II was mapped by use of anti-VP35 MAbs to the region between amino acid residues 167 and 278 of VP35. Amino acids 252-278 of VP35 might be involved in the formation of the epitopes for MAbs. B-cell epitopes were not found on the C-terminus of VP35 by use of PAbs or MAbs.

Animals↗
PubMed2001

Solution structure, domain features, and structural implications of mutants of the chromo domain from the fission yeast histone methyltransferase Clr4.

The encapsulation of otherwise transcribable loci within transcriptionally inactive heterochromatin is rapidly gaining recognition as an important mechanism of epigenetic gene regulation. In the fission yeast Schizosaccharomyces pombe, heterochromatinization of the mat2/mat3 loci silences the mating-type information encoded within these loci. Here, we present the solution structure of the chromo domain from the cryptic loci regulator protein Clr4. Clr4 is known to regulate silencing and switching at the mating-type loci and to affect chromatin structure at centromeres. Clr4 and its human and Drosophila homologs have been identified as histone H3-specific methyltransferases, further implicating this family of proteins in chromatin remodeling. Our structure highlights a conserved surface that may be involved in chromo domain-ligand interactions. We have also analyzed two chromo domain mutants (W31G and W41G) that previously were shown to affect silencing and switching in full-length Clr4. Both mutants are significantly destabilized relative to wild-type.

Amino Acid Sequence↗
PubMed2001

Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway.

In this study, we focus on different modes of regulation of STRA13, a human ortholog of the mouse basic helix-loop-helix transcriptional factor, previously identified by us as a new von Hippel-Lindau tumor suppressor gene (VHL) target. The gene was overexpressed in VHL-deficient cell lines and tumors, specifically clear cell renal carcinomas and hemangioblastomas. Introduction of wild type VHL transgene into clear cell renal carcinoma restored low level expression of STRA13. Overexpression was also detected in many common malignancies with an intact VHL gene, suggesting the existence of another, VHL-independent pathway of STRA13 regulation. Similar to many other von Hippel-Lindau tumor-suppressor protein (pVHL) targets, the expression of STRA13 on the mRNA level was hypoxia-sensitive, indicating oxygen-dependent regulation of the gene, presumably through the pVHL/hypoxia-inducible factor 1 (HIF-1) pathway. The yeast two-hybrid screening revealed interaction of the STRA13 protein with the human ubiquitin-conjugating enzyme (UBC9) protein, the specificity of which was confirmed in mammalian cells. By adding the proteasome inhibitor acetyl-leucinyl-leucinyl-norleucinal, we demonstrated that the 26 S proteasome pathway regulates the stability of pSTRA13. Co-expression of STRA13 and UBC9 led to an increase of the pSTRA13 ubiquitination and subsequent degradation. These data established that UBC9/STRA13 association in cells is of physiological importance, presenting direct proof of UBC9 involvement in the ubiquitin-dependent degradation of pSTRA13. Hypoxia treatment of mammalian cells transiently expressing STRA13 protein showed that stability of pSTRA13 is not affected by hypoxia or VHL. Thus, STRA13, a new pVHL target, is regulated in cells on multiple levels. We propose that STRA13 may play a critical role in carcinogenesis, since it is a potent transcriptional regulator, abundant in a variety of common tumors.

Basic Helix-Loop-Helix Proteins↗
PubMed2000

[The aged patient's first visit to the outpatient psychiatric clinic].

160 patients over 60 years of age appealed to gerontologic unit of out-patient psychiatric clinic for the first time. The patients were divided into two main groups: with organic mental disorders (OMD) and with functional mental disorders (FMD) (79 and 81 patients, respectively). In the group of OMD the main form of disturbances were cases with dementia (74.4%) mainly of the Alzheimer's type, and cerebral vascular dementia. In 25.3% of the patients the cognitive disturbances didn't attain the level of dementia. In a group of patients with different forms of dementia a high frequency of comorbid mental pathology was observed (83%)--confusional states, delusions, depressive conditions as well as disturbed behavior (67.7%) that was one of the reasons for consulting a psychiatrist. In FMD group the prevailing pathology were depressions, both of the major (37.1%) and mild (34.6%) forms. The remaining cases were characterized by delusions (10.1%), anxiety-phobic (7.6%) states and somatoform disturbances (5.1%). Among the patients both of OMD and FMD groups it was possible to diagnose approximately 3-4 different somatic diseases; vascular and gastrointestinal disorders were met more frequently. The study of contribution of brain computer tomography (CT) to diagnosis of mental pathology (according to ICD-10), has demonstrated that in 30.8% of the cases it was decisive, in 41% it confirmed the clinical data and in 21.8% CT provide additional data (detecting latent cerebral vascular damage). And only in 6.4% of the cases CT fails to give definite information in diagnostically complicated cases. In 26.6% of the patients with FMD, CT of brain had detected symptoms of mild vascular pathology.

Aged↗
PubMed1999

[Characteristics of the mitochondrial genome of russian germans].

Nucleotide sequences of the mitochondrial DNA (mtDNA) control region were studied in Germans living in the Altai, Russia. Although this ethnic group has been living in Russia for a long time, the obtained data indicate that its mitochondrial gene pool retains the main characteristics of the Western and Central European gene pools. Regarding the mitochondrial gene pool, Russian Germans were more similar to Germans living in Germany than to Russians with regard to the frequency of the Cambridge nucleotide sequence, frequencies and composition of five European haplotypic groups (classification of Richards et al.), and average intra- and interpopulation pairwise nucleotide differences. However, the mitochondrial gene pool of Altaian Germans also differed from that of Western European populations. The gene pool of Altaian Germans contained the ancestral variants of the main haplotypic groups. To date, these variants have not been found in modern Western and Central European populations, which is apparently due to their lower frequencies. In addition, some previously unknown mtDNA variants with specific nucleotide substitutions were found in Altaian Germans. The obtained results suggest that the modern mitochondrial gene pool of Europeans, including Germans from Germany, was largely affected by the demographic processes that occurred in the past two centuries. The Germans that lived in Russia were relatively isolated and, hence, retained more characteristics of the ancestral gene pool.

DNA, Mitochondrial↗
PubMed1998

Multiple epigenetic events regulate mating-type switching of fission yeast.

Two epigenetic events at mat1, one of which is DNA strand specific, are required to initiate recombination during mating-type switching. The third, a chromosomally borne imprinted event at the mat2/3 interval regulates silencing and directionality of switching, and prohibits interchromosomal recombination. We speculate that the unit of inheritance in the mat2/3 interval is both DNA plus its associated chromatin structure. Such a control is likely to be essential in maintaining particular states of gene expression during development.

Animals↗
PubMed1998

The chromo and SET domains of the Clr4 protein are essential for silencing in fission yeast.

Heritable inactivation of specific regions of the genome is a widespread, possibly universal phenomenon for gene regulation in eukaryotes. Self-perpetuating, clonally inherited chromatin structure has been proposed as the explanation for such phenomena as position-effect variegation (PEV) and control of segment determination and differentiation in flies, X-chromosome inactivation and parental imprinting in mammals, gene silencing by paramutation in maize and silencing of the mating-type loci in yeasts. We have now found that the clr4 gene, which is essential for silencing of centromeres and the mating-type loci in Schizosaccharomyces pombe, encodes a protein with high homology to the product of Su(var)3-9, a gene affecting PEV in Drosophila. Like Su(var)3-9p, Clr4p contains SET and chromo domains, motifs found in proteins that modulate chromatin structure. Site-directed mutations in the conserved residues of the chromo domain confirm that it is required for proper silencing and directional switching of the mating type, like SET domain. Surprisingly, RNA differential display experiments demonstrated that clr4+ can mediate transcriptional activation of certain other loci. These results show that clr4 plays a critical role in silencing at mating-type loci and centromeres through the organization of repressive chromatin structure and demonstrate a new, activator function for Clr4p.

Amino Acid Sequence↗
PubMed1994

Influence of protein calorie malnutrition and fasting on the activities of delta-aminolevulinic acid dehydratase and porphobilinogen deaminase in rats.

Rats were fed a restricted standard diet (6-8 g daily) for 4 weeks. The erythrocyte activity of delta-aminolevulinic acid dehydratase showed a very expressed decrease (7.9 times) and its hepatic activity diminished more than twice. Porphobilinogen deaminase activity was reduced by 40% and 17% respectively. After a 3-day total food deprivation delta-aminolevulinic acid dehydratase activity remained unchanged in red blood cells, but an increase by 52% was found in the liver. The erythrocyte activity of porphobilinogen deaminase was reduced by 42% and its hepatic activity--by 16%.

Animals↗
PubMed1994

[Restriction-deletion polymorphism of mitochondrial DNA region V in some populations of aboriginal residents of Siberia and the Far East].

The distribution of a deletion and of an Ava II site in region V of mitochondrial DNA (mtDNA) was studied in five populations of native inhabitants of the Asian part of Russia, including Chukchi, Asian Eskimos, Evenks, Buryats, and Northern Sel'kups. A deletion with a frequency of 6.3% was found only in Buryats, In Chukchi and Eskimos the AvaII site was not found. A maximal frequency of 11.3% was observed in the Evenks. A comparison with published data was conducted; it revealed a gradient of decreasing frequency of the deletion from Southeast Asia to the North, with its complete absence in the circumpolar regions. In the territory of northeast Asia, all three mitotypes are found, formed by a combination of two polymorphic markers of mtDNA region V, which were found earlier in humans in the New World. The data obtained necessitates a more detailed analysis of the population polymorphism of mtDNA in this region of Asia.

Base Sequence↗
PubMed1988

[Chronic compensated syndrome of disseminated intravascular coagulation in Sjögren's disease].

The authors have reported the results of investigations of the system of hemostasis in 40 patients with Sjogren's disease (SD) and 30 healthy donors. The SD patients had different disorders of the system of hemostasis resulting in the activation of the coagulative and anticoagulative systems. Chronic compensated DIC syndrome was shown to be present in approximately half of the SD patients. A positive therapeutic effect of prednisolone combined with heparin on chronic DIC syndrome was shown. It was assumed that microcirculatory and blood coagulation disorders could play an important role in a pathological process.

Chronic Disease↗