The long QT syndrome (LQTS) is a monogenic disorder characterized by prolongation of the QT interval on electrocardiogram and syncope or sudden death caused by polymorphic ventricular tachycardia (torsades de pointes). In general, mutations in cardiac ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) have been identified as a cause for LQTS. About 50-60 % of LQTS patients have an identifiable LQTS causing mutation in one of mentioned genes. In a group of 12 LQTS patients with no identified mutations in these genes we have tested a hypothesis that other candidate genes could be involved in LQTS pathophysiology. SCN1B and KCND3 genes encode ion channel proteins, ANK2 gene encodes cytoskeletal protein interacting with ion channels. To screen coding regions of genes SCN1B, KCND3, and 10 exons of ANK2 following methods were used: PCR, SSCP, and DNA sequencing. Five polymorphisms were found in screened candid ate genes, 2 polymorphisms in KCND3 and 3 in SCN1B. None of found polymorphisms has coding effect nor is located close to splice sites or has any similarity to known splicing enhancer motifs. Polymorphism G246T in SCN1B is a novel one. No mutation directly causing LQTS was found. Molecular mechanism of LQTS genesis in these patients remains unclear., M. Raudenská, A. Bittnerová, T. Novotný, A. Floriánová, K. Chroust, R. Gaillyová, B. Semrád, J. Kadlecová, M. Šišáková, O. Toman, J. Špinar., and Obsahuje bibliografii a bibliografické odkazy
The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition., S. B. Pajović, M. B. Radojčić, D. T. Kanazir., and Obsahuje bibliografii a bibliografické odkazy
Rhythmic daily changes in the Na,K-ATPase activity have been previously described for rat kidney cortex, showing two peaks: at 0900 h and 2100 h, and two valleys: at 1500 h and 0100 h - 0300 h. The oscillations in Na,K-ATPase activity are produced by an inhibitor, which binds the enzyme and is present in the rat blood plasma at valley times and absent or at very low concentrations at peak times. Since it has been demonstrated that active Na+ extrusion from the cells of several tissues depends not only on the Na,K-ATPase but also on the ouabain-insensitive Na-ATPase, we studied the activity of this latter enzyme of several rat tissues, i.e., kidney cortex, small intestine, liver, heart and red blood cells along the day. None of these tissues showed any variation of their Na-ATPase activity along the day. Preincubation of kidney cortex homogenates obtained at 0900 h, with blood plasma drawn at 0900 h and 1500 h, did not modify the Na-ATPase activity. Our results indicate that the Na-ATPase activity does not oscillate along the day. These results are in agreement with the idea that the Na-ATPase could partially compensate the Na+ transport affected by oscillations of the Na,K-ATPase activity., A. Reyes ... [et al.]., and Obsahuje seznam literatury
Komunikace mezi buňkami mnohobuněčného organismu je nezbytná k zajištění přežití organismu, správné funkce tkání a orgánů, tvorby energie, růstu a vývoje. Bílkoviny sekretované z buněk jsou hlavními molekulami, které zprostředkovávají mezibuněčnou komunikaci na malé i velké vzdálenosti. Většina sekretovaných bílkovin je z buněk uvolňována cestou přes endoplasmatické retikulum a Golgiho aparát. Vývoj nových laboratorních technik pro studium sekretovaných bílkovin umožnil v posledním desetiletí studovat a popsat sekreci mnoha typů buněk., Communication among cells in a multicellular organism is fundamental for the correct functioning of organs and tissues, energy production, growth and development, to assure survival and reproduction of the organism. Proteins secreted by cells are principal molecules for intercellular communication at both short and long distances. Most of the secreted proteins are released through the endoplasmic reticulum – the Golgi pathway. The significant development of analytical techniques for detection of secreted proteins in the last 10 years has enabled us to explore the secretion of various cell types., and Helena Kupcová Skalníková.
Metabolic consequences of direct muscle trauma are insufficiently defined. Their effects on the ubiquitin-proteasome pathway (UPP) of protein degradation in human skeletal muscles are as yet unknown. Thus, we investigated whether the UPP is involved in the metabolic response evoked in directly traumatized human skeletal muscles. Biopsies were obtained from contused muscles after fractures and from normal muscles during elective implant removal (control). As estimated by western blot analyses, concentrations of free ubiquitin and ubiquitin protein conjugates were similar in extracts from injured and uninjured muscles. Ubiquitin protein ligation rates were reduced after injury (1.5±0.2 vs. 1.0±0.15 fkat/μg; p=0.04). Chymotryptic-, tryptic- and caspase-like proteasome peptidase activities (total activity minus activity in the presence of proteasome inhibitors) increased significantly after trauma (p=0.04 - 0.001). Significant increases in total chymotryptic- and caspase-like activities were attributable to proteasome activation. Our results extend the possible role of the UPP in muscle wasting to direct muscle trauma. They further suggest that the effects of direct mechanical trauma are not limited to the proteasome and imply that ubiquitin protein ligase systems are also involved. Based on the potential role of the UPP in systemic diseases, it might also be a therapeutic target to influence muscle loss in critically ill blunt trauma patients, in which large proportions of muscle are exposed to direct trauma. and Obsahuje bibliografii a bibliografické odkazy
Oxidative stress has been implicated to play a major role in aging and age-related diseases. In the present study, we investigated the effects of aging on the total antioxidant capacity, uric acid, lipid peroxidation, total sulfhydryl group content and damage to DNA in adult (6 months), old (15 months) and senescent (26 months) male Wistar rats. The antioxidant capacity, determined by phycoerythrin-based TRAP method (total peroxyl radical-trapping potential) was significantly decreased in the plasma and myocardium of old and senescent rats, whereas plasma level of uric acid was elevated in 26-month-old rats. Age-related decline in plasma and heart antioxidant capacity was accompanied by a significant loss in total sulfhydryl group content, increased lipid peroxidation and higher DNA damage in lymphocytes. Correlations between TRAP and oxidative damage to lipids, proteins and DNA suggest that the decline in antioxidant status may play an important role in age-related accumulation of cell damage caused by reactive oxygen species., M. Sivoňová, Z. Tatarková, Z. Ďuračková, D. Dobrota, J. Lehotský, T. Matáková, P. Kaplán., and Obsahuje bibliografii a bibliografické odkazy
Retinol binding protein 4 (RBP4) is a novel adipokine which might be involved in the development of insulin resistance. The aim of the study was to investigate the expression of RBP4 mRNA in subcutaneous and visceral fat depots and the relationship between RBP4 plasma and mRNA levels relative to indices of adiposity and insulin resistance. In 59 Caucasian women (BMI 20 to 49 kg/m2 ) paired samples of subcutaneous and visceral fat were obtained for RBP4, leptin and GLUT 4 mRNA analysis using reverse transcription-quantitative PCR. Euglycemic hyperinsulinemic clamp and computed tomography scans were performed. RBP4 mRNA levels as well as GLUT 4 mRNA and leptin mRNA levels were lower (P<0.001, P<0.01 and P<0.001, respectively) in visceral compared to subcutaneous fat. No differences were found in RBP4 mRNA expression in the two fat depots or in RBP4 plasma levels between subgroups of non-obese subjects (n=26), obese subjects without metabolic syndrome (n=17) and with metabolic syndrome (n=16). No correlations between RBP4 mRNA or plasma levels relative to adiposity, glucose disposal rate and GLUT 4 mRNA expression in adipose tissue were found. There was a weak positive correlation between plasma RBP4 and plasma triglycerides (r = 0.30, p<0.05) and between plasma RBP4 and blood glucose (r = 0.26, p<0.05). Regardless of the state of adiposity or insulin resistance, RBP4 expression in humans was lower in visceral than in subcutaneous fat. We found no direct relationship between either RBP4 mRNA or its plasma levels and the adiposity or insulin resistance. and Obsahuje bibliografii a bibliografické odkazy
Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP leve ls were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels., D. Haluzíková ... [et al.]., and Obsahuje seznam literatury
This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid peroxidation, nitric oxide production and antioxidant systems in rats exposed to chronic restraint stress. Twenty four male Wistar rats, aged three months, were divided into four groups: control (C), the group treated with LA (L), the group exposed to restraint stress (S) and the group exposed to stress and treated with LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Restraint stress significantly decreased brain copper/zinc superoxide dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the control group. Thiobarbituric acid reactive substances (TBARS), nitrite and nitrate levels were significantly increased in the tissues of the S group compared with the C group. LA produced a significant decrease in brain and retina TBARS, nitrite and nitrate levels of the L and LS groups compared to their corresponding control groups. LA increased all enzyme activities in the tissues of the LS group compared to the S group. Our study indicated that LA is an ideal antioxidant candidate for the prevention of stress-induced lipid peroxidation., D. Akpinar, P. Yargiçoğlu, N. Derin, Y. Alicigüzel, A. Ağar., and Obsahuje bibliografii a bibliografické odkazy