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10th International Congress "Cell Volume Regulation: Novel Therapeutic Targets and Pharmacological Approaches"
IMMUNE EFFECTS OF THE STRESS EXPOSURES AND SUSCEPTIBILITY TO GLUCOCORTICOIDS IN INHERITED STRESS-INDUCED ARTERIAL HYPERTENSION RAT STRAIN WITH STRESS-SENSITIVE ARTERIAL HYPERTENSION
Tseilikman, V.E.1, Kozochkin, D.A.1, Sibiryak, S.V.1, Markel, A.L.2, Tseilikman, O.B.3, Nikitina, A.A.1, Komelkova, M.V.1, and Misharina, M.E.1
1 South Ural State Medical University, Chelyabinsk, Russian Federation
2 Institute of Cytology and Genetic, Novosibirsk, Russian Federation
3 South Ural State University, Chelyabinsk, Russian Federation
Activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis is regarded for one mechanism for the regulation of cell volume. Chronic or long-term stress as well as endogenous glucocorticoids at pharmacologic concentrations, and synthetic glucocorticoids can suppress immunity by decreasing immune cell numbers. Glucocorticoids decrease the immune cell numbers via induction of apoptosis especially in thymus. Male Wistar rats and male ISIAH (Inherited Stress-Induced Arterial Hypertension) rats were used in the study. Animals were exposed to four periods of repeated stress exposures by immobilization to a board. In the next experiments, stressed and unstressed rats were subcutane-ously injected by glucocorticoid drug Kenalog (dose 2 mg/kg) 24 hours after repeated stress exposures cessation.
Stress exposures caused significant elevation of the percentage of the apoptotic cell nuclei and decrease the percentage of thymocytes in the S/G2/M phase cells only in the ISIAH rats. Whereas in the Wistar rats were no significant differences in the percentage of the cells in the subdiploid, diploid and tetraploid DNA peaks. Previously stress exposures are completely preserve involution of thymus, apoptosis enhancement and the arrest of the thymocytes in the S/G2/M phase cells after Kenalog administration in ISIAH rats. In conclusion, we have shown that stress-mediated conditioning of the glucocorticoid secretion and responsiveness might represent a previously unrecognized mechanism that is involved in shaping immune response.
Supported by RFBR grant 11-04-01378-a.
THE USE OF SODIUM-FREE LITHIUM SOLUTION TO MODEL A CELL WITHOUT THE NA,K-ATPASE PUMP
Vereninov, I.A.1, Yurinskaya, V.E.2, and Vereninov, A.A.2
1 St. Petersburg State Polytechnic University, St. Petersburg, Russian Federation
2 Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation
Lithium can cross the cell membrane via almost every sodium route except the Na,K-ATPase pump. Cells in a sodium-free lithium medium rapidly lose internal sodium and thereafter behave as if without the pump, which can counteract accumulation of cations dominating the external solution. Therefore the ion and water balance in a cell as a double Donnan system is upset. It is known that it takes time for cell swelling to develop after the pump is inactivated. During the first stage, the external cations replace intracellular potassium; cell chloride and water content begin to increase later.
Modeling the monovalent ion redistribution is a rather difficult problem: it has been solved only for some special cases. We created a program for simulation of the monovalent ion redistribution following a balance disturbance for the cell model that includes the sodium pump, electroconductive ion channels of the Goldman type, and cotransporters NKCC, KCC and Na-Cl. The results of simulation were compared with the experimental data obtained on lymphoid U937 cells. It appears that kinetic parameters
found for the balanced state give satisfactorily results for non-stationary processes after the sodium pump stops. The similarity between the ion redistribution processes in cells treated with ouabain and with sodium-free lithium solution has been confirmed both in experiment and in simulation. The difference is that the ion disturbance in the lithium medium can be reverted (at least after 3 h). Simulation shows how the process of ion redistribution following pump inhibition depends on the cell type, which can be characterized by two parameters: the intracellular K+/Na+ ratio and the membrane potential. Simulation shows that the equivalent Li+/Na+ exchange in a sodium-free lithium solution can occur without specialized Li+/Na+ counter-transporters. The "lithium cell" model can be useful in understanding of the roles of sodium and potassium in the cell. It has been found, for instance, that in "lithium" U937 cells placed in hyperos-motic solutions the RVI response disappears whereas AVD persists. The study was supported by the RFBR grants no. 12-04-01669-a 09-04-00301a and by the Program №7 of the Presidium of RAS.
Бюллетень сибирской медицины, 2013, том 12, № 4, с. 24-68
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