Vol 11, No 1 (2017)

This review focuses on the effects of temperature on the functioning of the neuromuscular system. The changes in environmental temperature could affect the contractile acts in both ectotherms and endotherms by changing the amplitude and velocity of contractions and, accordingly, the mechanical work of skeletal muscles. In this study, we summarize the data on the effects of hypo- and hyperthermia on the supraspinal and peripheral components of regulation of the neuromuscular function.

The formation of hydrophilic pores in a lipid bilayer during phase transition is described using the Smoluchowski equation with an additional term of the hydrophobic pore source. This term is added to account for defects in lipid packing during phase transition. We assume that the temporal sequence of the pores is a stochastic process, a non-stationary second-order Erlang flow. Flow characteristics depend on the equation solution and determine the formation times of the hydrophilic pores. The calculated distribution of the durations of intervals between hydrophilic pores is in a good agreement with experimental data published before. In the context of this model we describe the influence of poly(ethylene glycol) on the pore formation frequency.

The ability of two synthetic peptides GEGEEGEE and DFGEEAEE to inhibit the invasiveness of tumor cells has been studied. Using confocal microscopy, it was demonstrated that these peptides specifically bind to receptor for hyaluronic acid mediated motility (RHAMM) on the prostate cancer cell surface. Effect of peptides on invadopodia formation in cancer cells was studied by fluorescent gelatin degradation. Using confocal microscopy, images of the cells were obtained and the degree of their invasiveness was analyzed by assessing the gelatin degradation area using ImageJ software. It was found that pre-incubation of tumor cells with the peptides at a concentration of 40 μg/mL (2 × 10^–7 M) inhibited the invasiveness by more than 80%. Thus, it was shown that peptides GEGEEGEE and DFGEEAEE may be potential antitumor agents.

Using a pyrene as a fluorescent probe, we investigated the influence of native and oxidized apolipoprotein A-I (apo A-I) and their complexes with tetrahydrocortisol (THC) on the microviscosity of the erythrocyte plasma membrane. The addition of THC to isolated membranes led to a 17% increase in the membrane microviscosity. In contrast, native apo A-I reduced the microviscosity (i.e., increased the fluidity) of the membranes by 15%. A more pronounced increase (by 25%) in the membrane fluidity was found in the presence of the complex of apo A-I with THC. Unlike native apo A-I, oxidized apo A-I and its complex with THC did not change the membrane viscosity. In view of the fact that apo A-I plays an important role in the binding of membrane cholesterol we suggest that the observed increase in the membrane fluidity under the influence of the native apo A-I is associated with the cholesterol efflux from plasma membrane. Oxidative modification of apo A-I likely disturbs the mechanisms of the cholesterol efflux and prevents the decrease in the membrane microviscosity.

The relationships between the red blood cell (RBC) membrane elasticity and RBC aggregation in healthy individuals and in patients with anemia of malignant tumors treated with human erythropoietin drug epoetin alfa (EA) were analyzed. It was found that prior to the treatment of patients, incubation of RBCs with EA was accompanied by an increase of RBC deformability and the reduction of their aggregation (RBCA). In these circumstances the two characteristics of the RBC microrheology correlated negatively with each other (r =–0.734, p < 0.05). In contrast, aggregation and deformability of RBCs from healthy individuals increased under the influence of EA and positively correlated with each other (r = 0.580, p < 0.05). After a 4-week treatment of patients with EA, aggregation response of the patients’ RBCs was increased by 29% (p < 0.05) and was close to that of healthy RBCs. This change of the RBC aggregation response may be connected with an alteration of the sensitivity of the membrane cationic channel to EA and an increase of the cell deformability. This possibility was supported by experiments with the use of Ca²⁺-channel blocker verapamil and Ca²⁺-chelating agent EDTA. Under these conditions a decrease of the RBC aggregation varied from 40 to 50% (p < 0.05). It was suggested that the effectors of calcium regulatory cascade upon exposure to EA may be membrane integrin receptors of type IIb–IIIa. This assumption was confirmed by experiments employing the inhibitors of these receptors (tirofibam and integrelin) and a preparation of monoclonal antibodies against IIb–IIIa receptors (monafram), which produced a significant decrease (20–30%, p < 0.05) of the RBC aggregation. Thus, our findings suggest that the altered aggregation response of RBCs in anemic patients with malignant tumors can be restored by the correction of anemia with epoetin alfa.

In this work, effects of manganese on respiration of rat liver mitochondria and the rate of K⁺ outflow from rat erythrocytes are studied in a broad range of concentrations. It is shown that manganese ions at low concentrations (1 × 10^–7–3 × 10^–5 М) inhibit K⁺ outflow from rat erythrocytes; this can be used to prevent their lysis. At high concentrations (1 × 10^–4–1 × 10^–3 M), manganese activates K⁺ outflow from the erythrocytes but inhibits the valinomycin-induced outflow of the ion from the erythrocytes. This fact is an indication of manganese influence on physicochemical properties of membranes. At low concentrations manganese does not affect parameters of respiration and oxidative phosphorylation of rat liver mitochondria, while at high concentrations it exerts acceleration of the mitochondrial respiration, i.e., uncouples respiration from phosphorilation and, hence, inhibits ATP synthesis.

Previously we have shown that at traumatic shock in rats the force of contraction of isolated aorta in response to angiotensin II, vasopressin, endothelin 1, or norepinephrine is decreased. On the contrary, vasoconstriction caused by serotonin is increased. A possible reason of the alterations of neuroendocrine regulation of vascular tone in shock may be a change in the expression of the receptors of these agonists in blood vessels. In the present study, using real-time PCR, we demonstrated that a day after injury the contents of mRNA encoding receptors V1A for vasopressin, ETA for endothelin 1, and AT1 for angiotensin II are not changed in aorta. There was a slight increase of the serotonin 5-HT2A receptor mRNA (36 ± 16%; p = 0.41). The level of the 5-HT2B receptor mRNA in aorta, initially low (2% of the content of the mRNA of receptors 5-HT2A), after the injury increased 15.8 ± 0.3 times (p < 0.01). However, at traumatic shock there was no contraction of aorta in response to 5-HT2B receptor agonist BW723C86, while vasodilation of the isolated aorta preconstricted with norepinephrine in response to BW723C86 was similar to that of the vessel isolated from control rats. The data obtained suggest that the observed 5-HT2B receptor overexpression is not related to the increased serotonin-induced vasoconstriction and might cause other vascular pathological changes at traumatic shock.