Promyelocytic leukemia protein (PML) knockout increases mitochondrial Ca uptake in HeLa cells.

The multifunctional promyelocytic leukemia protein (PML) is involved in the regulation of various cellular processes in both physiological and pathological conditions. Specifically, PML is one of the inositol-1,4,5-trisphosphate receptors (IPRs) activity regulators and can influence Ca transport from the endoplasmic reticulum (ER) to mitochondria. In this work, the effects of PML knockout on calcium homeostasis in the cytosol, ER, and mitochondria of HeLa cells were studied upon stimulation with histamine, which induces Ca mobilization from the ER via IPRs.

Ten Hypermethylated lncRNA Genes Are Specifically Involved in the Initiation, Progression, and Lymphatic and Peritoneal Metastasis of Epithelial Ovarian Cancer.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (, , , , , , , , , and ) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues ( < 0.

Phenols and GABA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae.

γ-Aminobutyric acid type A receptors (GABARs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which are widespread throughout the invertebrate and vertebrate central nervous system. GABARs are engaged in short-term changes of the neuronal concentrations of chloride (Cl) and bicarbonate (HCO ) ions by their passive permeability through the ion channel pore. GABARs are regulated by various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols.

Scanning Probe Microscopy Techniques for Studying the Cell Glycocalyx.

The glycocalyx is a brush-like layer that covers the surfaces of the membranes of most cell types. It consists of a mixture of carbohydrates, mainly glycoproteins and proteoglycans. Due to its structure and sensitivity to environmental conditions, it represents a complicated object to investigate.

[MicroRNA Biogenesis in Cell Senescence Induced by Chronic Endoplasmic Reticulum Stress].

MicroRNAs are small noncoding RNAs that regulate gene expression; stabilize the cell phenotype; and play an important role in cell differentiation, development, and apoptosis. A canonical microRNA biogenesis pathway includes several posttranscriptional steps of processing and transport and ends with cytoplasmic cleavage of pre-miRNA by type III ribonuclease DICER to form a mature duplex, which is included in RISC. MicroRNA biogenesis and role in cell stress are still poorly understood.

Protein Corona Attenuates the Targeting of Antitumor Sialyl Lewis X-Decorated Liposomes to Vascular Endothelial Cells under Flow Conditions.

Previously, we showed in the human umbilical vein endothelial cells (HUVECs) model that a liposome formulation of melphalan lipophilic prodrug (MlphDG) decorated with selectin ligand tetrasaccharide Sialyl Lewis X (SiaLe) undergoes specific uptake by activated cells and in an in vivo tumor model causes a severe antivascular effect. Here, we cultured HUVECs in a microfluidic chip and then applied the liposome formulations to study their interactions with the cells in situ under hydrodynamic conditions close to capillary blood flow using confocal fluorescent microscopy. The incorporation of 5 to 10% SiaLe conjugate in the bilayer of MlphDG liposomes increased their consumption exclusively by activated endotheliocytes.

Zinc Inhibits the GABAR/ATPase during Postnatal Rat Development: The Role of Cysteine Residue.

Zinc ions (Zn) are concentrated in various brain regions and can act as a neuromodulator, targeting a wide spectrum of postsynaptic receptors and enzymes. Zn inhibits the GABARs, and its potency is profoundly affected by the subunit composition and neuronal developmental stage. Although the extracellular amino acid residues of the receptor's hetero-oligomeric structure are preferred for Zn binding, there are intracellular sites that, in principle, could coordinate its potency.

[Protein Homeostasis Dysregulation in Pathogenesis of Neurodegenerative Diseases].

The formation and accumulation of unfolded, misfolded, or damaged cellular proteins leads to development of endoplasmic reticulum stress (ER stress). A series of protective reactions is initiated in response to ER stress. These reactions are aimed at restoring the balance between protein synthesis and degradation, which is key to maintaining protein homeostasis (proteostasis).

Physiological Role of ATPase for GABA Receptor Resensitization.

γ-Aminobutyric acid type A receptors (GABARs) mediate primarily inhibitory synaptic transmission in the central nervous system. Following fast-paced activation, which provides the selective flow of mainly chloride (Cl) and less bicarbonate (HCO) ions via the pore, these receptors undergo desensitization that is paradoxically prevented by the process of their recovery, referred to as resensitization. To clarify the mechanism of resensitization, we used the cortical synaptoneurosomes from the rat brain and HEK 293FT cells.

Dysregulation of lncRNA-miRNA-mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer.

Ovarian cancer (OC) is one of the most common types of cancer among malignancies of the female reproductive system. This pathology is asymptomatic until advanced stages and has a poor prognosis. Our study aimed to search for lncRNA-miRNA-mRNA competing triplets that promote ovarian tumorigenesis.

Ectopic GABA receptor β3 subunit determines Cl / -ATPase and chloride transport in HEK 293FT cells.

Neuronal intracellular chloride concentration ([Cl ] ) is a crucial determinant of transmission mediated by the γ-aminobutyric acid type A receptor (GABA R), which subserves synaptic and extrasynaptic inhibition as well as excitation. The Cl ion is the main carrier of charge through the GABA R; however, bicarbonate ions ( ) flowing in the opposite direction can also contribute to the net current. The direction of Cl and fluxes is determined by the underlying electrochemical gradient, which is controlled by Cl transporters and channels.

Changes in the Surface Expression of Intercellular Adhesion Molecule 3, the Induction of Apoptosis, and the Inhibition of Cell-Cycle Progression of Human Multidrug-Resistant Jurkat/A4 Cells Exposed to a Random Positioning Machine.

Experiments from flight- and ground-based model systems suggest that unexpected alterations of the human lymphoblastoid cell line Jurkat, as well as effects on cell growth, metabolism, and apoptosis, can occur in altered gravity conditions. Using a desktop random positioning machine (RPM), we investigated the effects of simulated microgravity on Jurkat cells and their multidrug-resistant subline, Jurkat/A4 cells. The viability of Jurkat/A4 cells decreased after simulated microgravity in contrast with the Jurkat cells.

Transcriptomic changes triggered by ouabain in rat cerebellum granule cells: Role of α3- and α1-Na+,K+-ATPase-mediated signaling.

It was shown previously that inhibition of the ubiquitous α1 isoform of Na+,K+-ATPase by ouabain sharply affects gene expression profile via elevation of intracellular [Na+]i/[K+]i ratio. Unlike other cells, neurons are abundant in the α3 isoform of Na+,K+-ATPase, whose affinity in rodents to ouabain is 104-fold higher compared to the α1 isoform. With these sharp differences in mind, we compared transcriptomic changes in rat cerebellum granule cells triggered by inhibition of α1- and α3-Na+,K+-ATPase isoforms.

Differential processing of small RNAs during endoplasmic reticulum stress.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program.

Detection of autoantibodies to potentially amyloidogenic protein, gamma-synuclein, in the serum of patients with amyotrophic lateral sclerosis and cerebral circulatory disorders.

In this study, we analyzed serum for the presence of antibodies to gamma-synuclein in patients with amyotrophic lateral sclerosis (ALS) compared to the control group of patients with other neurological diseases and healthy control donors. As a result, antibodies against gamma-synuclein are not an ALS-specific feature and have been identified in patients with ALS as well as in the control group patients. Patients with the impaired cerebral circulation showed increased incidence of autoantibodies to gamma-synuclein, yet the difference lacks statistical representativeness due to limited sample size.

Microfluidic droplet platform for ultrahigh-throughput single-cell screening of biodiversity.

Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species.

[Agonists of 5HT2C-receptors SCH 23390 and MK 212 incresase the force of rat aorta contraction in the presence of vasopressin and angiotensin II].

We investigated the role of 5HT2C receptors in regulation of blood vessel contractility. We determined expression of 5HT2C receptors in smooth muscle cell line A7r5 as well as on isolated rat aorta. It was shown that strong vasoconstriction effect of 5HT2C receptor agonists - SCH 23390 and MK 212 appeared on blood vessels after preliminary activation of angiotensin ATIA- and vasopressin V1A-receptors.

[The Effects of Inhibitors of Rho- and tyrosine c-Src-kinases on serotonin-induced constrictions of the aorta and mesenteric artery in rats].

We found that the inhibitor of Rho-kinase fasudil selectively inhibited constriction of isolated rings of the aorta and mesenteric artery in rats in response to application of the agonists of 5HT2A-(DOI and TBC-2) and 5HT1A-receptors (8-OH-DPAT) and did not influence vasoconstriction induced by serotonin. We demonstrate for the first time that application of the agonists of 5HT2C-receptors (MK 212 and SCH 23390) did not influence the tone of "intact" vessels. The marked vasoconstrictory effect of the agonists of 5HT2C-receptors was observed in the vessels preconstricted due to angiotensin II or vasopressin.

[Molecular logic of the endoplasmic reticulum stress signal pathways: the system of unfolded protein response].

Endoplasmic reticulum (ER) is the central organelle of a eukaryotic cell, it provides the synthesis and maturation of the majority of secretory and transmembrane proteins. The intensity of ER-related protein synthesis and ER loading varies in different cell types and depends on the cell microenvironment, physiological state of the cells, the stage of cellular differentiation. Quality control of transmembrane and secretory proteins in ER is a high precision process.

[Cluster analysis in biomedical researches].

Cluster analysis is one of the most popular methods for the analysis of multi-parameter data. The cluster analysis reveals the internal structure of the data, group the separate observations on the degree of their similarity. The review provides a definition of the basic concepts of cluster analysis, and discusses the most popular clustering algorithms: k-means, hierarchical algorithms, Kohonen networks algorithms.

[Total aminothioles of rat plasma under intraperitoneal and subcutaneous introduction of homocysteine].

In the presented work a variation of total aminothiols (cysteine, glutathione, cysteinylglycine and homocysteine) in blood plasma have been shown at modelling hyperhomocysteinemia by daily intraperitoneal (0.6 mkmol/g body weight) and subcutaneous (0.12 mkmol/g body weight) introduction of homocysteine.

[Induction of the endoplasmic reticulum stress in conditions of acid-base imbalance in human cells of T-lymphoblastic leukemia].

Endoplasmic reticulum stress - typical molecular pathophysiological process that underlies many cardiovascular, endocrine and other diseases. Violations of the protein conformational maturation processes in the endoplasmic reticulum can cause proteotoxic stress. Compensatory mechanisms are activated in response to ER stress include increased expression of enzymes involved in the formation of disulfide bonds in proteins.

[Deposition of von Willebrand factor in human endothelial cells HUVEC in the endoplasmic reticulum stress induced by an excess of homocysteine in vitro].

Von Willebrand factor (vWF) is an adhesive glycoprotein synthesized and secreted by endothelial cells and megakaryocytes. Violation of vWF secretion by endothelial cells is a characteristic feature of endothelial dysfunction in hyperhomocysteinemia. In our study we examined to clarify the concentration-dependent effect of homocysteine (Hcy) on the expression of vWF.

[Determination of reduced homocysteine fraction in blood plasma with HPLC-MS].

Homocysteine is a bioactive compound involved in many impotant processes of clinical significance. High sensitivity methods associated with preparation of oxidation-resistant derivatives are of demand for determination of different homocysteine fractions. In this work a derivatization agent N-ethylmaleinimide (NEM) was proposed by us for detection of reduced homocysteine fraction with HPLC-MS.