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Biomedical subjects

O V Smirnova

Publications and source records attributed to O V Smirnova.

At least 19 recordsLinked to original sources

Overexpression of prolactin receptors during intrahepatic transplantation of RS1 rat cholangiocellular carcinoma cells.

Immunohistochemical study showed that expression of prolactin receptors in intrahepatically transplanted cells of RS1 cholangiocellular carcinoma 2-fold exceeds that in cholangiocytes of intact rats. The number of prolactin receptors significantly increased in tumor cell nuclei of male and female animals. The RS1 transplant induced overexpression of prolactin receptors in hepatocytes and increased their number in nuclei of these cells.

Animals↗

Prolactin receptors in rat cholangiocytes: regulation of level and isoform ratio is sex independent.

The presence of prolactin receptor and peculiarities of its isoform expression in bile duct cells (cholangiocytes) differentially isolated from rat liver under different conditions were investigated in the present study. Normal cholangiocytes express prolactin receptor at relatively low level comparable to those of some prolactin-dependent tissues. Long receptor isoform is predominant in cholangiocytes but not in hepatocytes. The prolactin receptor level increases significantly under obstructive cholestasis due to evaluation of long and appearance of short isoforms. In rat cholangiocytes, unlike other tissues, the main positive regulators of prolactin receptor expression are cholestasis-induced factors instead of sex hormone and prolactin levels. Long isoform is predominant and induced primarily by cholestasis-induced factors.

Animals↗

Long isoform of prolactin receptor predominates in rat intrahepatic bile ducts and further increases under obstructive cholestasis.

Prolactin participates in the regulation of liver function. However, prolactin receptor (PrlR) expression and its regulation have been described only for hepatocytes. In this study, we investigated the expression and regulation of PrlR isoforms in the other important intrahepatic cellular compartment: the biliary epithelial cells, or cholangiocytes. Our aim was to determine whether prolactin should be considered as a potential regulator of cholangiocyte function under normal and pathological conditions. Cholangiocytes and hepatocytes were differentially isolated from rat liver. PrlR expression was analysed at the mRNA level by isoform-specific semiquantitative PCR, and at the protein level by immunostaining of liver sections. Hormonal regulation of PrlR expression was evaluated by comparing intact rats with gonadectomized, pituitary-grafted or bromocriptine-treated animals. Common bile-duct ligation was used as the experimental model of cholestasis. Our results demonstrate that the expression pattern and regulation of PrlR isoforms is totally different in cholangiocytes compared with hepatocytes: (1) mature rat cholangiocytes express low levels of PrlR, while it is very high in hepatocytes, (2) only the long isoform is detected in cholangiocytes, while the short isoform predominates in hepatocytes and (3) PrlR levels in cholangiocytes are induced by obstructive cholestasis, but not by sex hormones or prolactin, while it is the opposite in hepatocytes. From these data, the actions of prolactin on liver are anticipated to exhibit strong cell-type specificity in both normal and pathological conditions.

Animals↗

[Mechanisms of discrimation of the prolatin physiologic action on the liver at the receptor level of hepatocytes and cholangiocytes].

The role ofprolactin receptor isoforms in discrimination ofprolactin effects on liver is summarized. The necessity of studying of parameters ofprolactin receptor expression in differentially isolated different types of liver cells is demonstrated. The review is illustrated by data on different regulation by sex hormones and obstructive cholestasis of expression of prolactin receptor isoforms in rat hepatocytes and epithelial cells of bile ducts. The mathematical model is introduced for estimation of intensity of prolactin-induced signal cascades on the basis of experimentally measured parameters of prolactin receptor expression. Some further steps of the investigation of prolactin effects discrimination at the level receptor unit are suggested.

Animals↗

Short forms of membrane receptors: generation and role in hormonal signal transduction.

This review highlights the generation of various types of short forms of membrane hormonal receptors and the mode of regulation of their tissue-specific patterns. The short forms of membrane receptors are classified on the basis of localization of missing functional fragments. The review provides examples of tissues for which expression of short forms may serve as a marker of changes of ontogenetic stage, physiological state, or the development of pathological process. The short forms of receptors are shown to participate in determining tissue-specificity and efficacy of hormonal signal transduction, as well as in transport of hormones within cell, through physiological barriers, and in blood circulation. Peculiarities of signal transduction pathways for short receptor forms and potential physiological significance of these forms are analyzed. It is concluded that the ratio of long and short receptor forms may serve as a key marker of dynamic changes of differentiation stage and alterations of metabolic and proliferative activity of tissues under normal and pathologic conditions, and thus to be an important indicator of therapeutic effect for many pathological processes.

Alternative Splicing↗

Influence of obstructive cholestasis and sex hormones on the ratio of mRNA of two alternative prolactin receptor isoforms in rat hepatocytes.

The effects of obstructive cholestasis and sex hormones on the total content of prolactin receptor mRNA and ratio of mRNAs of its short and long isoforms have been studied in rat hepatocytes. Obstructive cholestasis caused insignificant changes in total content of prolactin receptor mRNA, but the proportion of mRNA of the long isoform increased. Comparison of prolactin receptor mRNA levels in gonadectomized and intact animals revealed opposite effects of male and female sex hormones on total mRNA, but both groups of these hormones increased the proportion of prolactin receptor short form mRNA. Changes in ratio of mRNA of receptor isoforms found in rat hepatocytes under obstructive cholestasis did not depend on levels of sex hormones. Obstructive cholestasis and sex hormones are suggested to regulate the content of long and short prolactin receptor isoforms in hepatocytes independently.

Animals↗

[The role of macrophages in asbestos-induced carcinogenesis].

Data available on the pathways of asbestos (fibrous) carcinogenesis still leaves much to be desired. Asbestos is regarded as a non-genotoxic substance by most researchers. There is insufficient evidence on the interaction of fibres, target-cells and macrophages. Macrophages secreted proteins (ca. 450 kD) to inhibit proliferation of intact mesothelium and cytoxine (3-5 kD) which stimulated the cellular sensitivity of intact mesothelium and mesotheliomas to the toxic influence of asbestos. It was suggested that the effect was due to the triggering of intrinsic causation of cell death. Like any other fibres, carcinogenic effect of asbestos could be accounted for by such significant factor as active oxygen radicals. When exposed to asbestos, both intact mesothelial and mesothelioma cells and macrophages synthesized those substances. Free radical-like substances in conjunction with macrophage-conditioned media produced toxic effect on mesothelial cells. The role of active oxygen radicals in fibre-induced carcinogenesis is discussed.

Animals↗

Comparative analysis of proteome maps of Helicobacter pylori clinical isolates.

The gram-negative bacterium Helicobacter pylori is found in human gastric mucosa. A widely distributed H. pylori infection is associated with chronic gastritis, gastric and duodenal ulcers, and malignant neoplasms. In this study proteome maps of four H. pylori clinical isolates derived from patients of two Russian regions (Moscow/Moscow Region and Novosibirsk) were obtained using 2D-electrophoresis and MALDI-TOF-mass-spectrometry. Variability of some H. pylori proteins and the level of their expression have been evaluated. These four isolates could be easily subdivided into two equal groups characterized by the close proteome profiles and the isolate from Moscow Region and the isolate from Novosibirsk constituted one group. The present study demonstrates the potential of proteome technology, which can be employed together with genome and transcriptome studies for the multiparameter typing of clinical isolates of pathogenic microorganisms.

Cell Extracts↗

Expression of prolactin receptors in human liver during cholestasis of different etiology and secondary liver cancer.

Indirect immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men. The intensity of expression was maximum in secondary liver cancer, high in obstructive jaundice of different etiology, and less pronounced in cholelithiasis. The expression of prolactin receptors in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice of different etiology. Cells of secondary tumors were characterized by low expression, while distant hepatocytes most intensively expressed prolactin receptors.

Adult↗

[Cloning and expression of the Mycoplasma hominis ftsZ for a cell division protein].

A Mycoplasma hominis chromosomal fragment containing the full-length ftsZ gene was cloned and sequenced. Natural expression of this gene was demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) with total RNA. The M. hominis FtsZ protein was shown to differ substantially from its counterparts of two other Mycoplasma species, M. genitalium and M. pneumoniae. The possibility of M. hominis ftsZ expression in Escherichia coli was demonstrated with several bacterial strains. The M. hominis FtsZ protein was isolated from E. coli cells transformed with recombinant plasmids carrying the M. hominis ftsZ gene. Complementation between the E. coli and M. hominis FtsZ proteins was observed in transformants.

Amino Acid Sequence↗

Characterization of the Mycoplasma hominis ftsZ gene and its sequence variability in mycoplasma clinical isolates.

We cloned and sequenced Mycoplasma hominis chromosomal fragment containing ftsZ gene. The wild-type expression of the gene was shown at RNA level by reverse transcription followed by PCR amplification. We revealed that M. hominis FtsZ had a comparatively low similarity to proteins of Mycoplasma genitalium and Mycoplasma pneumoniae. After full ftsZ gene sequencing for 14 clinical isolates of M. hominis, single-nucleotide substitutions were found in 21 positions, 6 of them being common for almost all isolates. This ftsZ gene polymorphism may be used for subtyping of M. hominis in clinical samples. Expression of the M. hominis ftsZ gene in different Escherichia coli strains was also demonstrated, and M. hominis FtsZ protein was purified from E. coli cells transformed with recombinant expression plasmid. Complementation between the M. hominis FtsZ and E. coli FtsZ could be shown. The comparison of FtsZ protein structures may also be used for investigation of bacterial phylogenetic relationships.

Amino Acid Sequence↗

[Development of fluoroquinolone (ciprofloxacin) resistance in Mycoplasma hominis in the presence of Hela cells].

The effect of cocultivation of eukaryotic HeLa cells and Mycoplasma hominis mycoplasma on the resistance of the latter to fluoroquinolones (ciprofloxacin) was examined. It was shown that cocultivation of the M. homonis and HeLa cells during 24 h with subsequent addition of ciprofloxacin resulted in an increase of the mircoplasma resistance to this antimicrobial agent. In the M. hominis cells cultivated in the presence of HeLa cells and the increasing concentration of ciprofloxacin mutations in the parC gene were observed only at low concentrations of the antimicrobial agent, while mutations in the gyrA gene were never detected. A gradual elevation of ciprofloxacin concentration up to 10 micrograms/ml resulted in the reversion of the parC mutations in mycoplasmas. Mycoplasma cells resistant to high flouroquinolone concentrations and isolated after cocultivation with the HeLa cells were characterized by the wild-type genotype in respect of the gyrA and parC genes. It was shown for the first time that infection of HeLa cells resulted in the appearance of genome rearrangements in M. hominis cells.

Anti-Infective Agents↗

Expression of prolactin receptors in rat reproductive tissues during periovulatory prolactin imbalance.

Indirect immunoperoxidase technique in combination with cytophotometry showed that prolactin imbalance in the periovulatory period is characterized by considerable changes in the expression of prolactin receptors in uterine glands and endometrial stroma (but not in the myometrium) and in the pituitary gland and hypothalamus, while receptor compartmentalization pattern remains unchanged.

Animals↗

A new level of hormonal signal transduction: primary nuclear action of protein and peptide hormones.

Contemporary data on the possibility of primary nuclear action of protein and peptide hormones are analyzed and summarized. Experimental data on the nuclear accumulation of protein and peptide hormones and their receptors, ligand dependence of nuclear translocation of membrane receptors, intranuclear distribution of membrane receptors, and dependence of nuclear accumulation of membrane receptors on the cell type are discussed. Evidence and hypothesis on the possible mechanisms of intracellular and transnuclear transport of protein and peptide hormones and their receptors, and association of nuclear translocation with cell proliferation are presented. Putative mechanisms of realization of the signal functions of protein and peptide hormones in the nucleus, including activation of autonomous nuclear signal cascades and phosphorylation of nuclear proteins, and the possibility of direct interaction of the nuclear pool of membrane receptors with transcription factors and DNA are analyzed. A possible biological role of primary nuclear action of protein and peptide hormones is discussed.

Animals↗