HPRT1 Deficiency Induces Alteration of Mitochondrial Energy Metabolism in the Brain.

Alterations in function of hypoxanthine guanine phosphoribosyl transferase (HPRT), one of the major enzymes involved in purine nucleotide exchange, lead to overproduction of uric acid and produce various symptoms of Lesch-Nyhan syndrome (LNS). One of the hallmarks of LNS is maximal expression of HPRT in the central nervous system with the highest activity of this enzyme in the midbrain and basal ganglia. However, the nature of neurological symptoms has yet to be clarified in details.

Current advances in gene therapy of mitochondrial diseases.

Mitochondrial diseases (MD) are a heterogeneous group of multisystem disorders involving metabolic errors. MD are characterized by extremely heterogeneous symptoms, ranging from organ-specific to multisystem dysfunction with different clinical courses. Most primary MD are autosomal recessive but maternal inheritance (from mtDNA), autosomal dominant, and X-linked inheritance is also known.

P2X7 Receptor and Purinergic Signaling: Orchestrating Mitochondrial Dysfunction in Neurodegenerative Diseases.

Mitochondrial dysfunction is one of the basic hallmarks of cellular pathology in neurodegenerative diseases. Since the metabolic activity of neurons is highly dependent on energy supply, nerve cells are especially vulnerable to impaired mitochondrial function. Besides providing oxidative phosphorylation, mitochondria are also involved in controlling levels of second messengers such as Ca ions and reactive oxygen species (ROS).

Evolution of Mechanical Stress () on Properties of Granulocytes in Acute Lymphoblastic Leukemia.

Acute lymphoid leukemia (ALL) affects the lymph cells or lymphocytes that make up the lymph tissue and prevents the proper maturation of the bone marrow cells. The processes through which cells convert mechanical stimuli into biochemical signals are called mechanical transitions and result in the sensation of specific cellular responses. In the present study, the functional properties of granulocytes of the patients with ALL were investigated using the mechanical stress model.

Measuring of Adhesion Force in the Cell-Cell System Based on Atomic Force Microscopy Technology.

We developed and tested a method for fabrication of a biosensor chip based on native human whole blood lymphocyte and a titanium tipless cantilever. The biosensor can be used for measuring intermolecular adhesion forces in the cell-cell system by using atomic force spectroscopy. The developed biosensor chip was applied for measuring adhesion force between lymphocyte and granulocyte and between lymphocyte and erythrocyte in healthy individuals and in patients with acute lymphoblastic leukemia (before treatment, during standard treatment, and during relapse).

Study of the properties of doxorubicin-resistant cells affected by acute leucosis.

The stiffness of cell membrane was found to be one of the factors determining resistance of a cell in vitro to antibiotic doxorubicin action. Membranes of surviving cells are negatively charged (-35 - -30 mV) and have high values of stiffness (2.2-5.

C60 fullerene affects elastic properties and osmoregulation reactions of human lymphocytes.

The influence of aqueous solution of pristine C60 fullerene (C60FAS) on functional activity of lymphocytes from a healthy person was studied for the first time. By means of atomic force microscopy, it was found that C60FAS in a concentration of 0.1 mg/ml increases the stiffness of the lymphocyte membrane by 41% (p < 0.

[Estimation of surface potential of lymphocytes from patients with leukemia using Kelvin probe mode].

The feasibilities of the Kelvin probe mode were shown to estimate a surface potential of lymphocytes from the patients with leukemia. Having compared the values of the surface potential obtained by the traditional method of microelectrophoresis and by the Kelvin probe mode, it was established that the use of the atomic force microscope made it possible to obtain data which were of specified diagnostic importance while studying lymphocyte functional status at different stages in leucopoiesis and indicated progression of the pathological process.

Effects of nanodispersed iron on the morphofunctional parameters of the blood system.

The effects of nanodispersed iron forms on the morphology and function of the blood system were studied. Maghemite and lepidocrocite caused a leukocytic shift towards segmented neutrophil forms, reduction of lymphocyte rigidity, and stimulated their compactization. In addition, the counts of small hyperchromatic erythrocytes with high rigidity increased in the blood flow.

The use of nanomechanic sensor for studies of morphofunctional properties of lymphocytes from healthy donors and patients with chronic lymphoblastic leukemia.

Tapping mode-atomic force microscopy and force spectroscopy were used for studies of the topography of the cell surface and elastic properties of lymphocytes from healthy donors and patients with chronic lymphoblastic leukemia. It was demonstrated that the decrease in lymphocytes stiffness in patients with chronic lymphoblastic leukemia by 51.4% (p<0.

[Structural and functional peculiarities of lymphocytes from patients with lymphoblastic leukemia].

New data on the structure and properties of the cell surface of lymphocytes from the blood of patients with CLL, ALL and ALL at remission stage has been obtained using AFM technologies. It's been shown that, despite the presence of immature lymphocytes in the blood flow of patients with CLL and ALL, the mechanical properties and geometrical parameters of the cells are different. Lymphocytes of CLL patients had an increased volume and higher stiffness, while the cells from the blood of patients with ALL and ALL in remission had decreased stiffness, which allowed the cells to spread on the substrate, thereby the volumes increased due to their reduced height and increased diameter.

[Osmoregulatory reactions of frog erythrocytes under conditions of activation and blockade of Ca2+-channels].

The kinetics of cell osmoregulatory reactions under conditions of activation and blockade of Ca2+-channels was studied on a model of frog polyfunctional nuclear erythrocyte. Both activation and blockade of Ca2+-channels has been established to promote swelling of nuclei and an increase of the nuclear-cytoplasmic ratios under conditions of hypotonic exposure. The osmoregulatory cell reactions after activation of Ca2+-channels are expressed as a decrease of the cell volume.

[Comparative estimation of morphofunction characteristics alive and fixed erythrocytes].

The method of power spectroscopy carries out the quantitative analysis of elastic properties of alive cells. It has been established that the highest indicators of elasticity nuclear (amphibious) and denuclearized (mammals) alive erythrocytes are registered in epi- and perinuclear space. When fixing with methanol and drying of cells the greatest values of the elastic modulus are displaced to the periphery of the cells.

Evaluation of morphometric parameters of native blood cells by atomic force microscopy.

We propose and tested a method for studies of native blood cells by atomic-force microscopy in a humid chamber preserving viability, size, and shape of biological objects. The method has some advantages over scanning in a liquid cell: it allows studying non-fixed blood samples in the form of suspension of live cells and excludes mechanical and chemical influences on the cells.

Nanotechnological approach to evaluation of mechanical properties of cell surfaces during stimulation and blockade of adrenoceptors.

We used a new nanotechnological approach for evaluation of functional activity of adrenoceptors during treatment of cell surfaces with various drugs. Local elasticity maps by nanoindentation points were constructed, which show the targets for drugs on transporter cells under natural conditions. The applied approach allowed identification of structural transformations in the membrane leading to changes in its elasticity, which can be used in cell physiology studies for controlling the processes of cell signaling.

[Seasonal activity of frog Rana ridibunda erythrocytes by data of electrophoretic mobility].

The peculiarities of frog erythrocytes electrophoretic mobility, coupled to the seasonal course of temperatures, have been studied. At the periods of anabiosis and of burst of hemopoiesis, in the vascular bed there increases the portion of functionally young erythrocytes (up to 28%) with increased values of the cell membrane surface charge. Preparation to hibernation is accompanied by a rise of the number of circulating functionally worn-down blood cells (up to 60%) with low values of the superficial charge and low mobility in electrical field.