Electrophysiological Features of Single Store-Operated Calcium Channels in HEK S4 Cell Line with Stable STIM1 Protein Knockdown.

An important role in intracellular calcium signaling is played by store-operated channels activated by STIM proteins, calcium sensors of the endoplasmic reticulum. In stable STIM1 knockdown HEK S4 cells, single channels activated by depletion of intracellular calcium stores were detected by cell-attached patch-clamp technique and their electrophysiological parameters were described. Comparison of the properties of single channels in HEK293 and HEK S4 cells revealed no significant differences in their current-voltage curves, while regulation of store-operated calcium channels in these cell lines depended on the level of STIM1 expression. We can conclude that electrophysiological peculiarities of store-regulated calcium entry observed in different cells can be explained by differences in STIM1 expression.

STIM1 Protein Activates Store-Operated Calcium Channels in Cellular Model of Huntington's Disease.

We have shown that the expression of full-length mutated huntingtin in human neuroblastoma cells (SK-N-SH) leads to an abnormal increase in calcium entry through store-operated channels. In this paper, the expression of the N-terminal fragment of mutated huntingtin (Htt138Q-1exon) is shown to be enough to provide an actual model for Huntington's disease. We have shown that Htt138Q-1exon expression causes increased store-operated calcium entry, which is mediated by at least two types of channels in SK-N-SH cells with different reversal potentials. Calcium sensor, STIM1, is required for activation of store-operated calcium entry in these cells. The results provide grounds for considering the proteins responsible for the activation and maintenance of the store-operated calcium entry as promising targets for developing novel therapeutics for neurodegenerative diseases.

[Effect of pineal peptides on the adrenal gland cortex glucocorticoid function and behavior in rats orally immunized with ovalbumin]. / Vliianie peptidov épifiza na gliukokortikoidnuiu funktsiiu kory nadpochechnikov i povedenie oral'no immunizirovannykh oval'buminom krys.

The influence of intraperitoneal injections of pineal peptides (5 mg/100 g of body mass during first five days of three weeks' oral immunization by ovalbumin) on the rats' behavior in the "open field" tests and on the blood corticosterone level, was investigated. It was found out that rats' oral immunization resulted in increasing of secretion activity of Peyer's patches antibody-producing cells, in decreasing of blood leukocyte cytokine-producing activity, in depression of the searching behavior and locomotor activity and in a significant (p < 0.05) lowering of the blood corticosterone level after 15 minutes in the "open field" tests. The pineal peptide injections caused an intensification of humoral immune response, a more obvious suppression of locomotor activity and searching behavior, and a significant decrease of the corticosterone level compared to the animals intraperitoneally injected by physiological solution. These data indicate that immuno-stimulative effect of pineal peptides combines with their ability to decrease glucocorticoid hormone secretion during stress-reaction.

The effects of epiphyseal peptides on the release of immunoglobulins in Peyer's patches in rats in vitro.

The effects of epiphyseal peptides (1 microg/ml) on the release of immunoglobulins into the incubation medium by isolated Peyer's patches from non-immunized mice and mice immunized orally against ovalbumin were studied during 40-min incubations. The possibility that epiphyseal peptides act on adrenoreceptors of cells in secondary lymphoid organs in the small intestine was assessed using alpha- and beta-adrenoreceptor blockers, i.e., phentolamine HCl (0.02 mg/ml) and anaprilin (0.06 mg/ml) respectively. Basal levels of secretory activity in control Peyer's patches from immunized rats were 2.4 times (p < 0.01) greater than for the lymphoid organs of non-immunized animals. The effects of epiphyseal peptides on the secretory activity of antibody-forming cells depended on the functional state of Peyer's patches. Application of epiphyseal peptides led to a 35% increase (p < 0.05) in the release of immunoglobulins from Peyer's patches in non-immunized rats and a 25% decrease (p < 0.05) in the release of antibody into the incubation medium from the lymphoid organs of immunized animals. These data lead to the suggestion that the activatory effect of epiphyseal peptides on antibody-forming cells in Peyer's patches from non-immunized animals is associated with alpha-adrenoceptors, while their inhibitory action on immunoglobulin release by the small intestine lymphoid organs from immunized animals is not mediated via adrenoceptors.

[The influence of pineal peptides on in vitro immunoglobulin secretion by Peyer's patches in rats]. / Vliianie peptidov épifiza na vydelenie immunoglobulinov peierovymi bliashkami krys in vitro.

The influence of the pineal peptides (1 mcg/ml) on immunoglobulin secretion by rat's Peyer's patches isolated from nonimmunized rats and from orally immunized by ovalbumin during 40 min incubation, was investigated. Using alpha- and beta-adrenoblockers--phentolamine hydrochloride (0.02 mg/ml) and anaprilin (0.6 mg/ml), respectively--the possibility of pineal peptides' effect on the gut secondary lymphoid organ' adrenoreceptors, was evaluated. Basic levels of immunized rats' control Peyer's patches secretory activity were 2.4--fold (p < 0.01) higher than those of non-immunized rats. The effect of pineal peptides on antibody-producing cells' secretory activity depended on Peyer's patches' functional condition. Application of pineal peptides led to a 35% (p < 0.05) increasing of immunoglobulin secretion by non-immunized rat Peyer's patches and to a 25% (p < 0.05) decreasing of antibody production by immunized rats lymphoid organs. These data suggest that the pineal peptides activation influence on Peyer's patches antibody-producing cells of nonimmunized rats connected with alpha-adrenoreceptors, and inhibiting action of these peptides on immunized rats lymphoid organs immunoglobulin secretion are not mediated through adrenoreceptors.

Melatonin increases both life span and tumor incidence in female CBA mice.

From the age of 6 months until their natural deaths, female CBA mice were given melatonin with their drinking water (20 mg/l) for 5 consecutive days every month. Intact mice served as controls. The results of this study show that the consumption of melatonin did not significantly influence food consumption, but it did increase the body weight of older mice; it did not influence physical strength or the presence of fatigue; it decreased locomotor activity and body temperature; it inhibited free radical processes in serum, brain, and liver; it slowed down the age-related switching-off of estrous function; and it increased life span. However, we also found that treatment with the used dose of melatonin increased spontaneous tumor incidence in mice. For this reason, we concluded that it would be premature to recommend melatonin as a geroprotector for long-term use.

[Effect of pineal peptide on parameters of the biological age and life span in mice]. / Vliianie peptida épifiza na pokazateli biologicheskogo vozrasta i prodolzhitel'nost' zhizni myshei.

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

[The effect of melatonin on the indices of biological age, on longevity and on the development of spontaneous tumors in mice]. / Vliianie melatonina na pokazateli biologicheskogo vozrasta, prodolzhitel'nost' zhizni i razvitie spontannykh opukholei u myshei.

Fifty female CBA mice were given melatonin with drinking water (20 mg/l) for 5 consecutive days monthly, beginning from the age of 6 months, until natural death. Another 50 intact mice were used as controls. Melatonin failed to significantly influence body weight or food consumption. Age-related switching-off of estrus function was delayed, body temperature decreased. Somewhat decreased motor activity did not affect physical one or endurance. Increase in life span led to higher spontaneous tumor incidence. Another experiment using 20 animals of the same line showed melatonin to inhibit free-radical processes. A conclusion was drawn that caution should be exercised before melatonin is recommended for long-term administration as a geroprotector.

Effect of vilon on biological age and lifespan in mice.

Subcutaneous administration of vilon (Lys-Glu) to female CBA mice starting from the 6th month of life increased physical activity and endurance, decreased body temperature, prolonged the lifespan, and prevented the development of spontaneous neoplasms. Vilon had no effect on age-related changes of estrous function and free radical processes. Long-term administration of vilon caused no unfavourable effects on animal development. The obtained results show safety of chronic vilon administration and allow to use this preparation for geroprotection and prophylaxis of age pathology.