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10th International Congress "Cell Volume Regulation: Novel Therapeutic Targets and Pharmacological Approaches"
THE ROLE OF THYROID HORMONES IN THE REGULATION OF OSMOTIC HOMEOSTASIS Dolomatov, S.I., Kubyshkin, A.V., and Satayeva, T.P.
Pathophysiology Department, Crimea State Medical University, Simferopol, Ukraine
Cell volume regulation is dependent from the efficiency of renal clearance of excess fluid and osmotically active substances (OAS). Thyroid hormones (TH) - one of the most important regulators of kidney function. In normal conditions excretion of OAS and fluids by kidneys depended from the glomerular filtration rate (GFR) and renal tubular transport. However, information about effects of TH on the GFR and renal excretion OAS is contradictory. In our investigation the effect of hypo- and hyperosmotic NaCl solutions on the GFR and renal excretion OAS in rats with different variants of thyroid status it was studied.
Results. In experiments use 72 Wistar rats. Episodic disturbance of thyroid status induced in rats by a single intragastric administration of thyroxine (T4) 50 mcg per 100 g of body weight. Renal function was investigated after intragastric administration of fluid in amount of 5% of body weight. Concentration of NaCl in the solution is from 0 to
3%. Water load in the rats with episodic disturbance of thyroid status leads to decrease GFR to 375 ± 19 versus control 542 ± 27 l/min (p < 0,01). Increased NaCl concentration was accompanied with progressive increase of GFR by the inclusion of renal functional reserve. In rats treated with T4 increase GFR detected only in group in which used 3% solution of NaCl. The level of osmolality of the extracellular fluid, the rate of excretion by the kidneys and the amount of urine OAS excretion in rats with loading by saline solutions had no significant differences between the control and rats treated with T4.
Conclusions. The kidneys of rats with episodic disturbance of thyroid status retain the ability to removal of excessive amounts of fluid and OAS, protecting tissues of internal organs from hypoosmotic state and hyperosmotic stress. In short term dysfunction of thyroid status changes in GFR and OAS tubular transport are reversible
THE ROLE OF TRPC CHANNELS IN DIFFERENTIATION AND PROLIFERATION - NEW TARGETS FOR CANCER TREATMENT
Elsholz, F.1' 2, Müller, W.E.2, and Leuner, K.1
1 Molecular & Clinical Pharmacy, Friedrich-Alexander University of Erlangen/Nuremberg, Erlangen, Germany
2 Insitute of Pharmacology, Goethe University, Biocenter, Frankfurt, Germany
The processes involved in the transformation of normal cells to cancer cells and in tumor progression are complex and only partly understood. Chronic infections and inflammation are major risk factors for various types of cancer. Neoplastic transformation is the result of the accumulation of mutations on certain key signaling proteins along with the formation and selection of aggressive cancer subclones. Among these key signaling proteins TRP channels have been identified to modulate a variety of physiological and pathological processes. Beside several TRPV channels e.g. TRPV1, and TRPM channels such as TRPM8 which might be involved in cancer pathology, TRPC6 channel expression was found to be significantly increased in prostate cancer tissue and in glioblastoma. However, several groups as well as our group showed that TRPC6 channels are essential for differentiation of cell types such as keratinocytes. Aberrant keratinocyte differentiation is considered to be a key mechanism in the onset
of hyperproliferative dermatological diseases, including basal cell carcinoma (BCC) the most common form of skin cancer. Mainly overexposure to sun light leads to DNA damage. Besides mutations, the local immune system is depressed, possibly decreasing immune surveillance for new tumor cells. Here, we wanted to investigate the interaction the immune system, keratinocyte differentiation and TRPC6 channel function and expression. We used IFNy, TNFa, IL4 and IL13 and investigated their effect on TRPC6 channel function after 24 h preincubation. Interestingly, all cytokines decreased TRPC6 mediated calcium influx in keratinocytes and also resulted in decreased TRPC6 channels expression. In addition, differentiation and proliferation were also attenuated by the cytokines. These first findings suggest interplay between inflammation and TRPC6 function and expression in keratinocytes. Further experiments need to clarify if these findings also play a role in the pathogenesis of basal cell carcinoma.
Бюллетень сибирской медицины, 2013, том 12, № 4, с. 24-68
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