MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease., D.-F. Li ... [et al.]., and Obsahuje seznam literatury
The aim of our study was to test the hypothesis, whether repeated allopurinol pre-treatment (in dose of 135 mg/kg s.c.) can influence changes of brain excitability caused by long-term hypoxia exposition in young immature rats. Rat pups were exposed together with their mother in to an intermittent hypobaric hypoxia (simulated altitude of 7 000 m) since the day of birth till the 11th day (youngest experimental group) or 17th day for 8 hours a day. Allopurinol was administered daily immediately before each hypoxia exposition. The duration of evoked afterdischarges (ADs) and the shape of evoked graphoelements were evaluated in 12, 18, 25 and 35-day-old freely moving male pups. Hypobaric hypoxia prolonged the duration of ADs in 12, 18 and 25-day-old rats. The ADs were prolonged in 35-day-old rats only after the first stimulation. Allopurinol shorted the duration of ADs only in 12-day-old pups. In older experimental group the effect of allopurinol treatment was less pronounced., K. Jandová, ... [et al.]., and Obsahuje seznam literatury
The negative affective state of opiate abstinence plays an important role in craving and relapse to compulsive drug use. The dopamine system participates in the reward effects of opiate use and the aversive effect of opiate abstinence. The amygdala is an essential neural substrate for associative learning of emotion. To establish a model of conditioned place aversion (CPA) in morphine-treated rats, we used different visual and tactual cues as conditioned stimuli (CS) within a conditioning apparatus. An injection of naloxone served as the unconditioned stimulus (US). The 6-hydroxydopamine (6-OHDA) lesion technique was used to investigate the effects of the dopaminergic system of the central nucleus of the amygdala (CeA) on naloxone-induced CPA. Rats were rendered physically dependent via administration of increasing doses of morphine delivered via intraperitoneal injection. Doses increased by 20 % each day for 14 days, starting from an initial dose of 6 mg/kg. All rats also received a low dose of naloxone (0.1 mg/kg) by injection 4 hours after morphine treatment on days 11 and 13 to induce CPA in a biased twocompartment conditioned place apparatus. Morphine-dependent rats with sham lesions were found to develop significant CPA after naloxone treatment. Bilateral 6-OHDA lesions of the CeA impaired the acquisition of CPA but had no effect on locomotor activity. These results suggest that the dopaminergic system of the CeA plays an important role in the negative affective state of opiate abstinence., W. Xu ... [et al.]., and Obsahuje seznam literatury
Uridine is postulated to participate in the development of insulin resistance. Since exercise is an effective tool in the treatment of insulin resistance it appeared justified to assess the impact of maximal exercise on plasma uridine and insulin sensitivity indices (e.g. insulin and HOMA-IR) in healthy subjects. The study included forty-four healthy males (18.5±2.92 years, VO2 max 50.2±6.26 ml kg-1 min-1). Subjects performed a single maximal exercise on a bicycle ergometer. Blood samples were taken three times: immediately before exercise, immediately after exercise and at the 30th min of rest. Uridine concentrations were determined in the whole blood using high-performance liquid chromatography. Serum insulin levels were measured by a specific ELISA method. Insulin sensitivity was assessed by homeostasis model assessment method (HOMA-IR). A maximal exercise-induced increase in the concentration of uridine correlated with post-exercise increases in insulin levels and HOMA-IR. Our results indicate a relationship between the concentration of uridine in the blood and indicators of insulin sensitivity in healthy subjects. We are the first to demonstrate that a maximal exercise-induced increase in the concentration of uridine is correlated with post-exercise increases in insulin levels and HOMA-IR in healthy subjects. It appears that uridine may be an indicator of insulin resistance., W. Dudzinska, ... [et al.]., and Obsahuje seznam literatury
Catalase is an antioxidant enzyme the activity of which is crucial for the protection against damage caused by reactive oxygen species. The –262C>T polymorphism in the promoter region of catalase gene was found to be associated with altered catalase levels. In this study, peripheral blood mononuclear cells catalase activity was measured after H2 O2-induced oxidative stress. C/T and T/T genotypes were associated with the decrease of catalase levels in contrast to C/C donors who had elevated catalase activity in the presence of 0.4 and 0.7 mM H2 O2. Genotypedependent response of catalase activity to oxidative stress might be related to the predisposition of catalase mutant allele carriers to disorders mediated by oxidative stress., A. V. Komina, ... [et al.]., and Obsahuje seznam literatury
Membrane fluidity is a widely recognized biophysical variable that provides information about structural organization of the subcellular membranes exhibiting physical characteristics of liquid crystals. The term “fluidity” reflects in this case the tightness in packing of acyl parts of the membrane phospholipid molecules, a feature that may influence considerably the molecular mobility and via that also the sensitivity and reactivity of membranebound transporters, receptors and enzyme systems. Data presented in this review are aimed to demonstrate the substantial role of changes in membrane fluidity occurring in the processes associated with endogenous protection observed in cardiac sarcolemma and mitochondria in diverse pathologies, particularly in diabetes and hypertension., A. Ziegelhöffer, ... [et al.]., and Obsahuje seznam literatury
Different mental operations were expected in the late phase of intracerebral ERPs obtained in the visual oddball task with mental counting. Therefore we searched for late divergences of target and nontarget ERPs followed by components exceeding the temporal window of the P300 wave. Electrical activity from 152 brain regions of 14 epileptic patients was recorded by means of depth electrodes. Average target and nontarget records from 1800 ms long EEG periods free of epileptic activity were compared. Late divergence preceded by almost identical course of the target and nontarget ERPs was found in 16 brain regions of 6 patients. The mean latency of the divergence point was 570±93 ms after the stimulus onset. The target post-divergence section of the ERP differed from the nontarget one by opposite polarity, different latency of the components, or even different number of the components. Generators of post-divergence ERP components were found in the parahippocampal gyrus, superior, middle and inferior temporal gyri, amygdala, and fronto-orbital cortex. Finding of late divergence indicates that functional differences exist even not sooner than during the final phase of the task., A. Damborská ... [et al.]., and Obsahuje seznam literatury
Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis., T. Štulc, M. Vrablík, Z. Kasalová, I. Marinov, H. Svobodová, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
During the early postnatal age environmental signals underlie the development of sensory systems. The visual system is considered as an appropriate system to evaluate role of sensory experience in postnatal development of sensory systems. This study was made to assess the effect of visual deprivation on strategy of arm selection in navigation of radial arm maze. Six-week-old light- (LR, control) and dark-reared (DR) rats were trained for correct choices and adjacent arms tasks. Our results showed that both the LR and DR animals equally selected correct arms. In the adjacent arms task, however, the control group significantly outperformed the DR animals. While the LR males and females displayed some differences in performing the tasks, no sex dependency was found in the performance of the DR group. These findings indicate that the lack of visual experience is likely to influence the strategy selection as well as sex differences. Thus the difference in the performance of LR and DR animals seems to be due to the male rather than female behavior., M. Salami., and Obsahuje bibliografii a bibliografické odkazy