- I have been working for more than 20 years in Riga Stradins University. I work in the field of molecular and cellular... moreI have been working for more than 20 years in Riga Stradins University. I work in the field of molecular and cellular biology, cancer epigenetics and biotechnology. A few years I worked in Karolinska Institute (Sweden). I have a collaboration with Sweden and Russian researchers.edit
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Prostate cancer (PCa) is a widespread oncological disease that proceeds in the indolent form in most patients. However, in some cases, the indolent form can transform into aggressive metastatic incurable cancer. The most important task of... more
Prostate cancer (PCa) is a widespread oncological disease that proceeds in the indolent form in most patients. However, in some cases, the indolent form can transform into aggressive metastatic incurable cancer. The most important task of PCa diagnostics is to search for early markers that can be used for predicting the transition of indolent cancer into its aggressive form. Currently, there are two effective preclinical models to study PCa pathogenesis: patients derived xenografts (PDXs) and patients derived organoids (PDOs). Both models have limitations that restrict their use in research. In this work, we investigated the ability of the primary 2D prostate cell cultures (PCCs) from PCa patients to express epithelial and cancer markers. Early PCCs were formed by epithelial cells that were progressively replaced with the fibroblast-like cells. Early PCCs contained tissue-specific stem cells that could grow in a 3D culture and form PDOs similar to those produced from the prostate ti...
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Small-scale plasmid DNA preparation or miniprep is a fundamental technique in estimation cloning experiments and is widely used for DNA methylation analysis in epigenetic research. Current plasmid DNA minipreps use alkali - SDS based... more
Small-scale plasmid DNA preparation or miniprep is a fundamental technique in estimation cloning experiments and is widely used for DNA methylation analysis in epigenetic research. Current plasmid DNA minipreps use alkali - SDS based method in a three-solution format and require the spin column-based purification steps. This procedure demands the vortexing or pipetting of pelleted by centrifugation bacteria and mixing of solutions manually. Here we describe a centrifuge/mixer-based instrument having an ability to perform centrifugation, vibration, and rotor oscillation in order to perform all steps of plasmid DNA isolation by device only. We found that applying rotor oscillation-driving mixing of solutions added in the lysis and neutralization steps, the homogeneous mixing is achieved within 5 second at rotor oscillation amplitude 45 degrees and oscillation frequency 400±30 rpm, yielding maximal quantity and quality of plasmid DNA. No increase of host chromosome presence in purified...
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The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were... more
The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were previously found to undergo prolonged G2 arrest with transient p53-dependent upregulation of opposing fate regulators, p21CIP1 (senescence) and OCT4A (self-renewal). Here we report on the analysis of the DNA methylation state of the distal enhancer (DE) and proximal enhancer (PE) of the <i>Oct4A</i> gene during this dual response. When compared to non–treated controls the methylation level increased from 1.3% to 12.5% and from 3% to 19.4%, in the DE and PE respectively. It included CpG and non-CpG methylation, which was not chaotic but presented two patterns in each enhancer. Discorrelating with methylation of enhancers, the transcription of <i>Oct4A</i> increased, however, a strong expression of the splicing form <i>Oct4B</...
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The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were... more
The epigenetic mechanisms underlying chemoresistance in cancer cells resulting from drug-induced reversible senescence are poorly understood. Chemoresistant ESC-like embryonal carcinoma PA1 cells treated with etoposide (ETO) were previously found to undergo prolonged G2 arrest with transient p53-dependent upregulation of opposing fate regulators, p21CIP1 (senescence) and OCT4A (self-renewal). Here we report on the analysis of the DNA methylation state of the distal enhancer (DE) and proximal enhancer (PE) of the Oct4A gene during this dual response. When compared to non-treated controls the methylation level increased from 1.3% to 12.5% and from 3% to 19.4%, in the DE and PE respectively. It included CpG and non-CpG methylation, which was not chaotic but presented two patterns in each enhancer. Discorrelating with methylation of enhancers, the transcription of Oct4A increased, however, a strong expression of the splicing form Oct4B was also induced, along with down-regulation of the...
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Parvovirus B19 (B19) is associated with a wide spectrum of diseases in humans, including autoimmune disorders and is possibly involved in the pathogenesis of some carcinomas. The appearance of B19 infection in non-permissive cells is... more
Parvovirus B19 (B19) is associated with a wide spectrum of diseases in humans, including autoimmune disorders and is possibly involved in the pathogenesis of some carcinomas. The appearance of B19 infection in non-permissive cells is poorly explored. Our study demonstrates that B19 virus is able to infect epithelial-like HOS TE85 cells. Although the virus particles were not found, the virus genomic DNA was detected in HOS cells during 3-11 passages. Moreover, the expression of B19 VP1 and NS1 mRNAs and the presence VP1/VP2 proteins were revealed in infected cells. The manifestation of B19 infection was dependent on virus dose. At the high dose (5000-8000 virus genomes/cell) massive apoptosis developed on the 6th day after infection and the cells were lost. Morphological and electron microscopy studies showed that the cytopathic effect was associated with apoptotic alteration in HOS cells. At the lower virus dose (100-1000 virus genomes/cell) the B19 infection in HOS cells was accomp...
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ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species. The N-terminal domain of ERp29 displays sequence and structural similarity to the protein disulfide... more
ERp29 is a soluble protein localized in the endoplasmic reticulum (ER) of eukaryotic cells, which is conserved in all mammalian species. The N-terminal domain of ERp29 displays sequence and structural similarity to the protein disulfide isomerase despite the lack of the characteristic double cysteine motif. Although the exact function of ERp29 is not yet known, it was hypothesized that it may facilitate folding and/or export of secretory proteins in/from the ER. ERp29 is induced by ER stress, i.e. accumulation of unfolded proteins in the ER. To gain an insight into the mechanisms regulating ERp29 expression we have cloned and characterized the rat ERp29 gene and studied in details its distribution in human tissues. Comparison with the murine and human genes and phylogenetic analysis demonstrated common origin and close ortholog relationships of these genes. Additionally, we have cloned approximately 3 kb of the 5'-flanking region of the ERp29 gene and functionally characterized ...
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Restriction-methylation enzymes BstN1 from Bacillus stearothermophilus were isolated and purified. These enzymes are related to a new class of restriction-methylation enzymes of the second type, whose modifying component is... more
Restriction-methylation enzymes BstN1 from Bacillus stearothermophilus were isolated and purified. These enzymes are related to a new class of restriction-methylation enzymes of the second type, whose modifying component is N4-cytosine-DNA-methylase. Both enzymes recognize the DNA sequence CC(A/T)GG. Restrictase BstN1 is a protein made up of one subunit with a molecular mass of 25 kDa. The molecular mass of native DNA-methylase BstN1 is about 55 kDa. The temperature optima for restrictase and methylase BstN1 are around 60 degrees C. Possible uses of BstN1 restriction-methylation enzymes for the analysis of cytosine methylation in bacterial and higher plant DNA are discussed.
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ABSTRACT
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Folding and post-translational modification of the thyroid hormone precursor, thyroglobulin (Tg), in the endoplasmic reticulum (ER) of the thyroid epithelial cells is facilitated by several molecular chaperones and folding enzymes, such... more
Folding and post-translational modification of the thyroid hormone precursor, thyroglobulin (Tg), in the endoplasmic reticulum (ER) of the thyroid epithelial cells is facilitated by several molecular chaperones and folding enzymes, such as BiP, GRP94, ...
Research Interests: Protein Folding, Chromatography, Biology, Biological Chemistry, Medicine, and 15 moreBiological Sciences, Liver, Thyroid gland, Animals, Biological, Endoplasmic Reticulum, Urea, CHEMICAL SCIENCES, Rats, Heat Shock Proteins, Protein Binding, Protein Denaturation, Ligands, Thyroglobulin, and Medical and Health Sciences
Research Interests: Protein Folding, Molecular endocrinology, Quality Control, Molecular, Unfolded Protein Response, and 15 moreEndoplasmic Reticulum, Rat Brain, Transcription Factor, Clinical Sciences, Enzyme activity, Veterinary Sciences, Heat Shock Protein, Congenital Hypothyroidism, Protein Binding, Intracellular Signaling, Immunoglobulin, Protein Transport, Tissue Specificity, protein disulfide isomerase (PDI), and Paediatrics and reproductive medicine
Research Interests: Kinetics, Transcription Factors, Molecular chaperones, Thyroid gland, Animals, and 11 moreUnfolded Protein Response, Endoplasmic Reticulum, Transcription Factor, Rats, Epithelial cells, Time Factors, Epithelial Cell Biology, DNA binding proteins, Biochemistry and cell biology, Chaperone, and Medical biochemistry and metabolomics
ERp29, a novel and ubiquitously expressed endoplasmic reticulum (ER) stress-inducible protein, was recently isolated and cDNA cloned in our laboratory. Using size exclusion chromatography and chemical cross-linking we have assessed the... more
ERp29, a novel and ubiquitously expressed endoplasmic reticulum (ER) stress-inducible protein, was recently isolated and cDNA cloned in our laboratory. Using size exclusion chromatography and chemical cross-linking we have assessed the oligomerization properties of ERp29. Purified ERp29 in solution as well as in rat hepatoma cells self-associates predominantly into homodimers. Labeling of the cells with [35S]methionine with subsequent cross-linking and
Research Interests: Biology, Endoplasmic Reticulum Stress, Medicine, Biopolymers, Animals, and 15 moreEndoplasmic Reticulum, ER stress, Enzyme, Thioredoxin, Rats, Heat Shock Proteins, Amino Acid Sequence, Recombinant Proteins, Protein Binding, Size Exclusion Chromatography, Biochemistry and cell biology, Molecular Sequence Data, Secondary structure prediction, cDNA cloning, and Sequence similarity
Cancer cells are committed to an actively secretory state that facilitates communication with their microenvironment. We have addressed the role of ERp29, a novel endoplasmic reticulum secretion factor in mammary carcinogenesis using... more
Cancer cells are committed to an actively secretory state that facilitates communication with their microenvironment. We have addressed the role of ERp29, a novel endoplasmic reticulum secretion factor in mammary carcinogenesis using MCF-7 human breast cancer cells as a model. Xenografts originating from cells stably transfected with dominant-negative form of ERp29 were smaller and better differentiated than those derived from cells overexpressing wild-type ERp29. Similar effects were observed by siRNA-mediated ERp29 silencing in xenografts. However, unlike xenografts, the modulation of ERp29 in vitro did not affect the rate of cell proliferation. In addition, we have evaluated the expression of ERp29 in the resting and lactating mammary glands of mice as well as in the human primary breast tumors. About 25% of breast cancers and also lactating mammary glands were expressing ERp29 while the resting glands did not. Taken together these data suggest the active involvement of ERp29 in the malignant conversion of mammary epithelial cells.
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Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic... more
Membrane penetration of nonenveloped viruses is a poorly understood process. We have investigated early stages of this process by studying the conformational change experienced by polyomavirus (Py) in the lumen of the endoplasmic reticulum (ER), a step that precedes its transport into ...