Mitochondria as an energy generating cell device are very sensitive to oxidative damage. Our previous findings obtained in hepatocytes demonstrated that Complex I of the respiratory chain is more sensitive to oxidative damage than other respiratory chain complexes. We present additional data on isolated mitochondria showing that palmityl carnitine oxidation is strongly depressed at a low (200 μM) tert-butyl hydroperoxide (tBHP) concentration, while oxidation of the flavoprotein-dependent substrate - succinate is not affected and neither is ATP synthesis inhibited by tBHP. In the presence of tBHP, the respiratory control index for palmityl carnitine oxidation is strongly depressed, but when succinate is oxidized the respiratory control index remains unaffected. Our findings thus indicate that flavoprotein-dependent substrates could be an important nutritional factor for the regeneration process in the necrotic liver damaged by oxidative stress., Z. Červinková, H. Rauchová, P. Křiváková, Z. Drahota., and Obsahuje bibliografii a bibliografické odkazy
The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto- caval fistula (ACF) in Hannover Sprague -Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP -450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis -4-[4-(3-adamantan -1-yl- ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg /l in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and m yocardial EETs to levels observed in sham -operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin -converting enzyme inhibition (ACEi, trandolapril, 6 mg /l in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume o verload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin -angiotensin system in the circulating blood and kidney tissue., L. Červenka, V. Melenovský, Z. Husková, A. Sporková, M. Bürgelová, P. Škaroupková, S. H. Hwang, B. D. Hammock, J. D. Imig, J. Sadowski., and Obsahuje bibliografii
We analyzed the effect of FK 506 on the production of nitric oxide by macrophages. Isolated rat peritoneal macrophages were cultured for 24 h with or without lipopolysaccharide (LPS) (5 µg/ml) and in the absence or presence of FK 506 (0.1 and 1 µg/ml). The concentration of NO2- in culture supernatants was taken as a measure of nitric oxide production. FK 506 (0.1 and 1 µg/ml) reduced the LPS-induced increase of NO2- levels by 68 % and 81 %, respectively. The impact of cyclosporin A (CsA) was studied in order to compare their effects. CsA (0.1 and 1 µg/ml) decreased the levels of nitrites by 39 % and 69 %, respectively. The results obtained suggest that both immunosuppressive drugs exhibit a dose-dependent inhibitory effect on nitric oxide production and that FK 506 is a more potent agent than CsA in this respect., P. Střeštíková, B. Otová, M. Filipec, H. Farghali., and Obsahuje bibliografii
Using high-resolution oxygraphy, we tested the changes of various parameters characterizing the mitochondrial energy provision system that were induced by peroxidative damage. In the presence of succinate as respiratory substrate, 3 mM t-butyl hydroperoxide increased respiration in the absence of ADP, which indicated partial uncoupling of oxidative phosphorylation. Low activity of coupled respiration was still maintained as indicated by the ADP-activated and oligomycin-inhibited respiration. However, during the incubation the phosphorylative capacity decreased as indicated by the continuous decrease of the mitochondrial membrane potential. Under these experimental conditions the maximum capacity of the succinate oxidase system was inhibited by 50 % in comparison with values obtained in the absence of t-butyl hydroperoxide. Our data thus indicate that the oxygraphic evaluation of mitochondrial function represents a useful tool for evaluation of changes participating in peroxidative damage of cell energy metabolism., P. Křiváková, A. Lábajová, Z. Červinková, Z. Drahota., and Obsahuje bibliografii a bibliografické odkazy
In contrast to the well-established anti-apoptotic effect of Bcl-2 protein, we have recently demonstrated that Bcl-2 overexpression by vaccinia virus causes apoptosis in BSC-40 cells, while it prevents apoptosis in HeLa G cells. Given the key role of mitochondria in the process of apoptosis, we focused on effects of Bcl-2 expression on mitochondrial energetics of these two cell lines. In this study we present data indicating that BSC-40 cells derive their ATP mainly from oxidative phosphorylation whereas HeLa G cells from glycolysis. More importantly, we show that in both cell lines, Bcl-2 inhibits mitochondrial respiration and causes a decrease of the ATP/ADP ratio. However, it appears that BSC-40 cells cannot sustain this decrease and die, while HeLa G cells survive, being adapted to the low ratio of ATP/ADP maintained by glycolysis. Based on this observation, we propose that the outcome of Bcl-2 expression is determined by the type of cellular ATP synthesis, namely that Bcl-2 causes apoptosis in cells relying on oxidative phosphorylation., M. Vrbacký, J. Krijt, Z. Drahota, Z. Mělková., and Obsahuje bibliografii
Aim of the study was to evaluate serum levels of insulin-like growth factor binding protein-3 in patients with liver cirrhosis and to compare serum IGFBP-3 levels with other liver function tests. Fifty-one patients with liver cirrhosis were selected for our study. We measured IGFBP-3 (1.67±1.06 mg/l, mean ± SD), albumin (32±8 g/l), prealbumin (0.22±0.14 g/l), AST (2.29±2.38 mkat/l), ALT (2.11±4.83 mkat/l) and cholinesterase (mean 78.6±45.2 mkat/l) in the serum. There was a significant positive correlation of serum IGFBP-3 with serum albumin and serum cholinesterase. The correlation coefficient was much lower between serum IGFBP-3 and serum prealbumin. There was no significant correlation between serum AST, ALT and IGFBP-3. Serum IGFBP-3 proves to be a better marker for the hepatic synthetic capacity than serum albumin or cholinesterase., K. Šídlová, M. Pechová, K. Kotaška, R. Průša., and Obsahuje bibliografii
Our previous study showed that a diet enriched with 400 g of carp per week improved plasma lipids in subjects after aortocoronary bypass (CABG). The aim of the present study is to determine whether the differe nt carp farming systems have an impact on the effects of carp meat in secondary cardiovascula r prevention. We examined 3 groups of patients after CABG over a 4-week period of spa treatment (108 persons, 73 males, 35 females, age over 60 years). We found no differences in baseline values of blood pressure or plasma lipids. The patients were given a standard spa diet (controls; N=36) or a diet enriched of 400 g of car p meat per week, enriched omega-3 (N=37) or cereal carp (N=35). Plasma lipid parameters were examined at start and after 4 weeks in a routine laboratory setting. Group consuming omega-3 carp showed the largest decline in total cholesterol, LDL ch olesterol, triglycerides and an increase in HDL cholesterol (all p<0.01). We found that carp meat from the two production systems showed significantly different effects on plasma lipids. Further t rials should be performed to clarify the exact causes of the differences., J. Mraz, T. Zajic, P. Kozak, J. Pickova, P. Kacer, V. Adamek, I. Kralova Lesna, V. Lanska, V. Adamkova., and Obsahuje bibliografii
Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6±11.9 mm Hg in SHR and 117.3±6.9 mm Hg in Wistar rats (P<0.01). The significant difference in BP increase to two doses of noradrenaline (0.1μg and 1 μg) between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7±2.0 mm Hg and 60.5±3.9 mm Hg and in Wistar rats 7.4±1.9 mm Hg and 40.5±3.2 mm Hg (P<0.01). The hypotensive response to acetylcholine (0.1 μg, 1 μg and 10 μ) in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9±10.2 mm Hg, 87.5±11.8 mm Hg and 103.4±10.6 mm Hg, while in Wistar rats it was 37.4 4.2 mm Hg P<0.0), 62.3±3.5 mm Hg (P<0.01) and 73.5±2.8 mm Hg (P<0.05). In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks., M. Gerová, F. Kristek., and Obsahuje bibliografii a bibliografické údaje
The two i nferior colliculi (IC) are paired structures in the midbrain that are connected to each other by a bundle of commissural fibers. The fibers play an important role in coordinating sound signal processing between the two inferior colliculi. This study examined inter-collicular suppression on sound signal processing in amp litude domain of mice by measuring the rate-amplitude functions (RAFs) of neurons in one IC during the electrical stimulation of the opposite IC. Three types (monotonic, saturated and non-monotonic) RAFs of collicular neurons were measured before and durin g inter-collicular suppression. Inter-collicular suppression significantly increased the slope, decreased the dynamic range and narrowed down the responsive amplitude of all RAFs to high amplitude level but did not change the type of most (36/43, 84 % ) RAFs. As a result, all types of RAFs were compressed at a greater degree at low than at high sound amplitude during inter-collicular suppression. These data indicate that inter-collicular suppression improve sound processing in the high amplitude domain., Liang Cheng, Hui-Xian Mei, Yun Huang., and Obsahuje bibliografii