Steroids are important components in the pathophysiology of Alzheimer’s disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5α-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD., M. Vaňková, M. hill, M. Velíková, J. Včelák, G. Vacínová, P. Lukášová, D. Vejražková, K. Dvořáková, R. Rusina, I. Holmerová, E. Jarolímová, H. Vaňková, B. Bendlová., and Obsahuje bibliografii
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein ki nase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of isch emia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166±40; AS 1.6±0.2 vs . 550±60 and 3.2±0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92±25; AS 1.7±0.2; P<0.05 vs . non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24±1.2 % as compared with 9 ± 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart., T. Ravingerová, J. Matejíková, D. Pancza, F. Kolář., and Obsahuje bibliografii
Diabetes mellitus is the leading cause of cardiovascular morbidity and mortality. Phlorizin (PHLOR) and quercetin-3-O-glucoside (QUER-3-G) are two natural compounds reported to have antidiabetic properties by inhibiting sodium/glucose transporters. Their effects on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin (STZ)-induced diabetic rats were investigated. Video edge detection and fluorescence photometry were used to measure ventricular myocyte shortening and intracellular Ca2+, respectively. Blood glucose in STZ rats was 4-fold higher (469.64±22.23 mg/dl, n=14) than in Controls (104.06±3.36 mg/dl, n=16). The amplitude of shortening was reduced by PHLOR in STZ (84.76±2.91 %, n=20) and Control (83.72±2.65 %, n=23) myocytes, and by QUER-3-G in STZ (79.12±2.28 %, n=20) and Control (76.69±1.92 %, n=30) myocytes. The amplitude of intracellular Ca2+ was also reduced by PHLOR in STZ (82.37±3.16 %, n=16) and Control (73.94±5.22 %, n=21) myocytes, and by QUER-3-G in STZ (73.62±5.83 %, n=18) and Control (78.32±3.54 %, n=41) myocytes. Myofilament sensitivity to Ca2+ was not significantly altered by PHLOR; however, it was reduced by QUER-3-G modestly in STZ myocytes and significantly in Controls. PHLOR and QUER-3-G did not significantly alter sarcoplasmic reticulum Ca2+ in STZ or Control myocytes. Altered mechanisms of Ca2+ transport partly underlie PHLOR and QUER-3-G negative inotropic effects in ventricular myocytes from STZ and Control rats., N. N. Hamouda, M. A. Qureshi, J. M. Alkaabi, M. Oz, F. C. Howarth., and Obsahuje bibliografii
Expression of the muscle phenotype is the result of interaction between intrinsic and extrinsic factors, the latter including innervation, mechanical influences and hormonal signals. This minireview summarizes some of the current knowledge regarding the regulation of myosin heavy chain (MHC) isoform transitions during muscle development and regeneration. It describes the role of genetic factors, neural and mechanical influences and it focuses on the contribution of thyroid hormones to the differentiation of muscle fiber phenotypes as shown by the regulation of the expression of MHC isoforms and development of myofibrillar ATPase activity. Finally, it shortly summarizes results regarding the differentiation of MHC isoforms in regenerated muscle fibers of the graft after heterochronous isotransplantation in rats with different thyroid status., T. Soukup, I. Jirmanová., and Obsahuje bibliografii
We tested the effects of epidermal growth factor (EGF) on Na+/H+ exchanger (NHE) activity using urogastrone for treatment of Wistar rats and rat kidney tissue slices. NHE activity was monitored in isolated kidney brush border membrane vesicles by following fluorescence quenching of acridine orange. A significant increase of NHE activity was detected as early as 5 min after addition of urogastrone to rat kidney slices in vitro. In Wistar rats treated with urogastrone we also found increased NHE activity (by about 12 %). Both changes of NHE activity were the result of a significant rise of Vmax value and an apparent decrease in Km value in in vitro experiments. The rise of NHE activity caused by urogastrone was sensitive to the inhibitors of transcription and translation. The presence of phosphatase inhibitor, NaF, elevated NHE activity of non-stimulated as well as of urogastrone-stimulated exchanger, suggesting that phosphorylation plays an important role in Na+/H+ exchange. Osmolarity of the medium seems to regulate NHE activity in such a manner that both hyper- and hypoosmolar conditions inhibited NHE activity. The absence of Ca2+ions produced a 60 % decrease of NHE activity. The chemical modification of histidine residues with diethyl pyrocarbonate or SH groups with N-ethylmaleimide inhibited NHE activity., K. Barišić, O. Karužić, J. Petrik, T. Ž. Grubišić., and Obsahuje bibliografii
The colorectum (late distal colon) is innervated by the sympathetic nervous system, and many colorectal diseases are related to disorders of the sympathetic nervous system. The sympathetic regulation of colorectal ion transport is rarely reported. The present study aims to investigate the effect of norepinephrine (NE) in the normal and catecholamine-depleted condition to clarify the regulation of the sympathetic adrenergic system in ion transport in the rat colorectum. NE-induced ion transport in the rats colorectum was measured by short-circuit current (Isc) recording; the expression of β-adrenoceptors and NE transporter (NET) were quantified by real-time PCR, and western blotting. When the endogenous catecholamine was depleted by reserpine, the baseline Isc in the colorectum was increased significantly comparing to controls. NE evoked downward ∆Isc in colorectum of treated rats was 1.8-fold of controls. The expression of β 2 -adrenoceptor protein in the colorectal mucosa was greater than the control, though the mRNA level was reduced. Ho wever, NET expression was significantly lower in catecholamine-depleted rats compared to the controls. In conclusion, the sympathetic nervous system plays an important role in regulating basal ion transport in the colorectum. Disorders of sympathe tic neurotransmitters result in abnormal ion transport, β-adrenoceptor and NET are involved in the process., X. Zhang, Y. Li, X. Zhang, Z. Duan, J. Zhu., and Obsahuje bibliografii
MicroRNAs (miRNAs) are a class of short non-coding regulatory RNA molecules which play an important role in intracellular communication and cell signaling and which influence cellular processes such as proliferation, differentiation, and cellular death. Over the past two decades, the crucial role of m icroRNAs in controlling tissue homeostasis and disease in cardiovascular systems has become widely recogni zed. By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis. The stability of miRNAs within the blood suggests that circulating miRNAs may function as important biomarkers of disease development and progression. Numerous circulating miRNAs have been found to be dysregulated in a wide variety of different disease states, including diabetes, cancer, and cardiovascular disease., D. Dlouhá, J. A. Hubáček., and Obsahuje bibliografii
The present study was focused on regulatory role of nitric oxide on functional properties of the cardiac Na, K-ATPase in three various animal models of hypertension: spontaneously hypertensive male rats (SHR) with increased activity of nitric oxide synthase (NOS) by 60 % (Sh1), SHR with decreased activity of NOS by 40 % (Sh2) and rats with hypertension induced by L-NAME (40 mg/kg/day) with depressed activity of NOS by 72 % (LN). Studying the utilization of energy substrate we observed higher Na, K-ATPase activity in the whole concentration range of ATP in Sh1 and decreased activity in Sh2 and LN. Evaluation of kinetic parameters revealed an increase of Vmax value by 37 % in Sh1 and decrease by 30 % in Sh2 and 17 % in LN. The KM value remained unchanged in Sh2 and LN, but was lower by 38 % in Sh1 indicating increased affinity of the ATP binding site, as compared to controls. During the activation with Na+ we observed increased Vmax by 64 % and increased KNa by 106 % in Sh1. In Sh2 we found decreased Vmax by 40 % and increased KNa by 38 %. In LN, the enzyme showed unchanged Vmax with increased KNa by 50 %. The above data indicate a positive role of increased activity of NOS in improved utilization of ATP as well as enhanced binding of Na+ by the cardiac Na, K-ATPase., J. Vlkovičová, V. Javorková, L. Mézešová, O. Pecháňová, N. Vrbjar., and Obsahuje bibliografii a bibliografické odkazy
Cigarette smoking is a risk factor for many diseases. It could be associated with sarcopenia. The aim of this meta-analysis was to determine whether smoking is an isolated risk factor for sarcopenia. We searched PubMed, Web of Science, EBSCO, and Science Direct for articles addressing the relationship between cigarette smoking and sarcopenia. A total of 12 studies containing information on 22,515 participants were included in this meta-analysis. Odds ratio (OR) was calculated for each study group and for all studies together. An OR was also calculated separately for each sex. We used a fixed-effect model in overall estimation and in males, because results of small studies were significantly different from the results of large studies in those cases and in females where the estimation showed only moderate heterogeneity we used a random-effect model. According to proposes of the Cochrane Handbook for Systematic Reviews. The resulting OR in the fixed-effect model was 1.12 (95 % CI 1.03-1.21), OR for each sex was in the fixed-effect model 1.20 (95 % CI 1.06-1.35) in males and in the randomeffect model 1.21 (95 % CI 0.92-1.59) in females. The results of this meta-analysis indicate that cigarette smoking as an isolated factor may contribute to the development of sarcopenia. However, the results of the individual studies were largely inconsistent due to different approaches of measuring the main variables which affected the results., M. Steffl, R. W. Bohannon, M. Petr, E. Kohlikova, I. Homerova., and Obsahuje bibliografii
Although the relationships between thyroid function and anthropometric parameters were studied in patients with thyroid disorders and in morbidly obese subjects, such data in normal healthy population are scarce. In our study, relationships between factors of body composition, fat distribution and age with hormones of the pituitary-thyroid axis were evaluated in a large, randomly selected sample of normal adult Czech population comprising of 1012 men and 1625 women. Our results exhibited weak, but significant relationships between body composition, body fat distribution and the parameters of pituitary-thyroid axis. Some of these associations were gender-specific. As shown by backward stepwise regression model, body fat distribution evaluated by centrality index (subscapular/triceps skinfold ratio) was negatively associated with free triiodothyronine (fT3) serum levels only in women, while a positive correlation of fT3 with BMI was specific for men. BMI was inversely related to free thyroxine (fT4) concentrations in women but not in men. The centrality index (CI) was positively related to TSH levels in both genders. The fT3/fT4 ratio, reflecting deiodinase activity, was inversely related to age and positively related to BMI in both genders, while the highly significant negative correlation between CI and fT3/fT4 ratio was specific for women., M. Dvořáková, M. Hill, J. Čeřovská, Z. Pobišová, R. Bílek, P. Hoskovcová, V. Zamrazil, V. Hainer., and Obsahuje bibliiografii a bibliografické odkazy