BackgroundRenalase is a recently discovered secretory protein involved in regulation of arterial blood pressure in humans and animals. Results of animal experiments from independent laboratories indicate that administration of human recombinant renalase decreases blood pressure and some genetically predisposed hypertensive rats have lowered renalase levels.Material/MethodsThe levels of renalase mRNA expression in brain hemispheres, heart, and kidneys of spontaneously hypertensive rats (SHR) with moderate (140–180 mm Hg) or high (>180 mm Hg) hypertension and of control Wistar-Kyoto (WKY) rats were analyzed using real-time PCR.ResultsSpontaneously hypertensive rats with high hypertension (>180 mm Hg) had a lower renalase mRNA level in brain hemispheres, and higher heart and kidney renalase mRNA levels compared with control WKY rats. In SHR with a moderate increase in arterial blood pressure (140–180 mm Hg), the tissue renalase mRNA changed in the same direction but did not reach the level of statistical significance as compared with control rats.ConclusionsThe results indicate that the development of hypertension in SHR is accompanied by altered expression of the renalase gene in the examined organs as compared with control WKY rats. The brain and peripheral tissues renalase mRNA levels demonstrate opposite trends, which are obviously crucial for impaired regulation of blood pressure in SHR.
The accumulation of ATP by preparations of plasma membranes enriched particles (PMEP) isolated from rat hepatocytes, murine splenocytes and human T-lymphocytes has been investigated after the binding of human and murine tumour necrosis factors (TNFct) to their specific receptors. The TNFc~-induced expression of the nuclear oncogene c-myc in intact hepatocytes has been also studied. TNFc~ induced the marked biosynthesis of ATP on PMEP of hepatocytes and splenocytes within the first minute of incubation. The biosynthesis of ATP was independent of the activity of adenylate kinase and only occured in the presence of all the components of aerobic phosphorylation and the electron acceptor, cytochrome C or diferric transferrin. The level of ATP on PM correlated with the degree of expression of the nuclear oncogene c-myc in the same target cells. Adriamycin totally suppressed the biosynthesis of ATP on PM and simultaneously inhibited the expression of c-myc. The ATP synthesized on PM is suggested to be involved in transduction of the proliferative or growth signal to the cell nucleus.
In order to develop a diagnostic panel, mRNA levels of tumor marker genes have been evaluated in capillary blood of patients with various malignant tumors of the gastrointestinal tract (GIT) by means of the method of reverse transcription combined with real-time PCR with detection of reaction products using TaqMan probes. Use of small volumes of capillary blood did not decrease sensitivity of this method. RNA expression of telomerase (mhTERT), alpha-fetoprotein (mAFP), carcinoembryonic antigen (mCEA) and cytokeratin-20 (mCK-20) was higher in most patients with tumors. Blood of donors or non-oncological patients contained much lower (trace) amounts of the RNA markers. The RNA markers are characterized by reasonably high specificity and sensitivity acceptable for diagnostic application. The mhTERT marker was the most universal one and exhibited the highest specificity and sensitivity. Combined determination of several RNA markers increased sensitivity of this method. It is concluded that determination of RNA markers in small volumes of capillary blood may be used for screening, primary diagnostics, and postoperative monitoring.
Plasma membranes of target cells generate considerable amounts of ATP in response to binding of growth factors, cytokines, and oncoproteins. Plasma membrane ATP is formed at the stage of ligand-receptor signal transduction by the anaerobic pathway with the involvement of plasma membrane redox systems and Na* (but not adenylate cyclase). The assumption on the involvement of transitory reversed Na+,K+-ATPase in the synthesis of plasma membrane ATP is confirmed by inhibitory analysis. ATP-producing activity of plasma membrane-enriched particles isolated from various target cells in response to various growth factors was studied. The formation of plasma membrane ATP is stimulated by growth factors and cytokines interacting with integral tyrosine kinase receptors or soluble tyrosine kinases in the cytosol. Various tyrosine kinase inhibitors act by utilizing plasma membrane ATP. Plasma membrane ATP is assumed to be a messenger and amplifier of ligand-receptor signals in plasma membranes of animal cells. Key Words: plasma membrane; ATP; growth factors; transmembrane signaling; oncogenesisPhosphorylation is the main mechanism responsible for induction or suppression of cell activity and realization of the major biological processes. Disturbances in the regulation of this mechanism cause a number of diseases [6,13,22,38,39].A new class of hormone-like compounds, polypeptide growth factors and cytokines involved in proliferation, differentiation, and transformation of many types of cells, including immunocompetent cells, was discovered over the past decades [19,34] [26,27]. A general concept of the main mechanism of transmission and amplification of extracellular signals for cell growth, proliferation, mitogenesis, differentiation, and chemotaxis perceived by membrane receptors was derived from these data.Tyrosine kinases play the major role in the transduction of receptor-mediated extracellular signals for cell growth, proliferation, differentiation, and oncogenesis [31][32][33]54]. Extracellular signals are transduced by intracellular messengers coupled with the corresponding protein kinases. However, the central mechanism responsible for activation of tyrosine kinases remains unclear. HistoryIn 1980, it was shown that the preparation of plasma membrane-enriched particles (PMEP) from rat skeletal muscles in a medium containing Tris-HCl (pH 7.5),
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