Redox regulation of copper-metallothionein

Copper (Cu) is an essential element whose localization within cells must be carefully controlled to avoid Cu-dependent redox cycling. Metallothioneins (MTs) are cysteine-rich metal-binding proteins that exert cytoprotective effects during metal exposure and oxidative stress. The specific role of MTs, however, in modulating Cu-dependent redox cycling remains unresolved. Our studies utilized a chemically defined model system to study MT modulation of Cu-dependent redox cycling under reducing (Cu/ascorbate) and mild oxidizing (Cu/ascorbate + H2O2) conditions. In the presence of Cu and ascorbate, MT blocked Cu-dependent lipid oxidation and ascorbyl radical formation with a stoichiometry corresponding to Cu/MT ratios 相似文献   

Cerebral responses of healthy humans to rhythmic transcranial magnetic stimulation of different intensities

The effect of rhythmic transcranial magnetic stimulation (rTMS) of different intensities (single superthreshold rTMS more intense than 1.2 T and subthreshold one with an intensity of 70–80% of the motor threshold) of sagittal premotor cortical areas on the human functional activity was estimated in eight volunteers on the basis of combined EEG, neuropsychological, and hemodynamic examinations. The objectives of the study included the selection of the frequency of activating stimulation and revision of the objective EEG criteria of rTMS efficiency. It has been demonstrated that analysis of the EEG response to photostimulation at different frequencies is efficient in selecting the rTMS frequency. The EEG coherence is one of the most informative characteristics of the rTMS effect on central neurodynamics. The functional effects of stimulation (activating or inhibitory) have been shown to depend on the initial level of intercentral coherent relationships It has been found that rTMS of the sagittal premotor cortex causes definite changes in the functional activity of a healthy brain different from those caused by placebo. These changes are greater in the left hemisphere (in the form of intrahemispheric changes in coherence and depend on the stimulation intensity (superor subthreshold) and the initial state. The vascular factor has been shown to play an important role in the formation of cerebral responses to rTMS.     

Features of Temporal Differentiation of the Chum Salmon Oncorhynchus ketaof the Anadyr Bay Region at Different Abundance Levels

The temporal heterogeneity of chum salmon stock of the Anadyr Bay region was investigated on the basis of a set of discrete external morphological features and fluctuating asymmetry level of some meristic structures. Differentiation of Anadyr Bay chum salmon during the spawning run was found to be associated with the abundance level of spawning stock in a particular year. Sharply pronounced temporal heterogeneity, based on the investigated characteristics, in the area near the river mouth can be considered as an indicator of the subsequent deficiency of spawners on the spawning grounds of rivers in the Anadyr Bay region.     

Effect of triethanolamine and silatranes on thermotolerance and accumulation of stress proteins in pea seedlings

A capability of triethanolamine (TEA) and its organosilicon derivatives methyl-, chloromethyl-, and ethoxy silatrane (MS, CMS, and ES, respectively) in low and ultra-low concentrations (from 10^?3 to 10^?13 M) to increase pea (Pisum sativum L.) thermotolerance and the relation of this process with heat-shock protein (HSP) accumulation in the roots were studied. Low and ultra-low concentrations of CMS and MS improved seedling survival under conditions of the heat shock (45°C). This process was not accompanied by stress protein accumulation. ES and CMS affected seedling survival and HSP accumulation differently in dependence on the temperature and preparation concentration.     

Lipid second messengers and cell signaling in vascular wall

Agonists of cellular receptors, such as receptor tyrosine kinases, G protein-coupled receptors, cytokine receptors, etc., activate phospholipases (C(gamma), C(beta), A(2), D), sphingomyelinase, and phosphatidylinositol-3-kinase. This produces active lipid metabolites, some of which are second messengers: inositol trisphosphate, diacylglycerides, ceramide, and phosphatidylinositol 3,4,5-trisphosphate. These universal mechanisms are involved in signal transduction to maintain blood vessel functions: regulation of vasodilation and vasoconstriction, mechanical stress resistance, and anticoagulant properties of the vessel lumen surface. Different signaling pathways realized through lipid second messengers interact to one another and modulate intracellular events. In early stages of atherogenesis, namely, accumulation of low density lipoproteins in the vascular wall, cascades of pro-atherogenic signal transduction are triggered through lipid second messengers. This leads to atherosclerosis, the general immuno-inflammatory disease of the vascular system.     

Influence of the human blood serum on contractility and beta-adrenoreactyvity of the isolated human myocardium

On strips of the isolated myocardium of right hearts auriculum of the 43 patients with ischemic illness of heart and 9 patients with heart diseases of various ethyology at statement venous canule during aorto-coronary shunting, estimated influence of adrenaline (10(-9)-10(-4) g/ml) on amplitude caused by electrostimulus (1H, 5ms, 25-30 V) contractions, and also inotropic and adrenomodulation activity of serum blood (in dilution 1 : 10000, 1: 1000, 1 : 500, 1: 100, 1 : 50, 1: 10 and 1 : 5) nonpregnant women. Direct dependence of amplitude of contraction on size of fraction of of blood emission on Teyholts is revealed. It means, that strips of right auriculum myocardium reflect contractility of a left ventriculum myocardium. Adrenaline in concentration 10(-7)-10(-6) g/ml dependent of dose raised amplitude of the caused contraction not influencing it in concentration of 10(-9) and 10(-8) g/ml (the constant of dissotiation has 2 x 10(-7) g/ml), that as a whole, speaks about decrease in efficiency of activation beta-AP. Blood Serum in dissolutions 1 : 10000-1 : 50 did not influence on amplitude of contraction, and in dissolutions 1 : 10 and 1 : 5 strengthened it, that speaks presence in blood the endogenous activator of myocyte contractility (EAMC). Serum showed beta-adrenomodulation activity that speaks presence in it endogenous sensitizer of beta-adrenoreceptors (ESBAR) and endogenous blocker of beta-adrenoreceptors (EBBAR). In particular, in experiences with adrenaline in subthreshold concentration (10(-8) g/ml) serum showed ESBAR-activity (in dissolutions 1 : 1000, 1 : 500, 1 : 100 and 1 : 50), and in experiences with adrenaline in as much as possible effective concentration (10(-6) g/ml) serum showed ESBAR-activity (in dissolutions 1 : 50 and 1 : 10) and EBBAR-activity (in dissolutions 1:500) Hence, containing in blood serum endogenous modulators of beta-adrenoreactivity - ESBAR and EBBAR can modulate efficiency of beta-adrenoreceptors activation of human cardiomyocytes. It speaks about perspectivity of application of ES BAR analogues in cardiology.     

Soluble glycoprotein 130 is inversely related to severity of coronary atherosclerosis

Purpose: Recent studies indicate that the effects of interleukin 6 (IL-6) realized via soluble IL-6 receptor (sIL-6R) facilitate the development of various pathological processes. Soluble gp130 (sgp130) is a naturally occurring inhibitor of signal transduction via this pathway. In this study, we assessed the relationship between circulating levels of IL-6, sIL-6R and sgp130 and severity of coronary atherosclerosis in patients with stable coronary artery disease (CAD).

Methods: Plasma levels of IL-6, sIL-6R and sgp130 were measured in patients with atherosclerotic coronary lesions (n?=?128, group 1) and with intact coronary arteries (n?=?48, group 2). The severity of coronary atherosclerosis was evaluated by the number of affected arteries and by Gensini Score index.

Results: Circulating IL-6 levels in group 1 were significantly higher than those in group 2. The levels of sIL-6R did not differ considerably in both the groups. The levels of sgp130 in group 1 were significantly lower than in group 2. A negative correlation has been revealed between sgp130 levels and the number of affected coronary arteries and Gensini Score index.

Conclusions: Serum concentration of sgp130 in patients with stable CAD is inversely related to severity of coronary damage. Low sgp130 level may serve as an additional indicator of coronary atherosclerosis severity.     

Secretory phospholipase A2 activity in blood serum: The challenge to sense

Excess levels of secretory phospholipase A2 (sPLA2) is known to contribute to several inflammatory diseases including vascular inflammation correlating with coronary events in coronary artery disease. Thus a method to monitor sPLA2 activity in blood serum is urgently needed. Such method is still a challenge since existing fluorescent probes do not allow to monitor sPLA2 activity directly in blood serum. Here we analyze and overcome barriers in sPLA2 sensing methodology and report a fluorescent probe and a kinetic model of its hydrolysis by sPLA2. New probe is designed with a fluorophore and a quencher not interfering binding to the enzyme. At the same time phospholipid matrix bearing the probe promotes efficient initial quenching of the fluorophore. Kinetic model of probe hydrolysis takes into account signal change due to the side processes. The probe and the kinetic model applied together prove the concept that the activity of sPLA can be measured directly in blood serum.     

The catalytically active secretory phospholipase A2 type IIA is involved in restenosis development after PTCA in human coronary arteries and generation of atherogenic LDL

Secretory phospholipase A₂ type IIA (sPLA₂) may actively contribute to atherogenesis, acting either within the arterial wall or in plasma. Proinflammatory eicosanoids and lysophospholipids, generated through hydrolysis of cell membrane phospholipids by sPLA₂, initiate and prolong the inflammatory process. In the present study we examined the possible involvement of sPLA₂ in development of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). We also investigated whether serum sPLA₂ could catalyze accumulation of lysophosphatidylcholine (LPC) in LDL. Concentrations and catalytic activities of sPLA₂ were measured in blood serum of 49 consenting patients immediately before, 1–7 and 180 days after PTCA. All patients had repeat angiograms at 180-day follow-up. Restenosis was registered in 19 patients. Accumulation of LPC in LDL was evaluated by thin-layer chromatography after incubation of blood serum with LDL. Serum sPLA₂ concentrations increased in all study patients by day 1 post-PTCA, but the increase was significantly greater and more protracted in patients who developed restenosis. Catalytic activities increased significantly 6 days post-PTCA in patients who developed restenosis, whereas for patients without restenosis there was no change in serum sPLA₂ activity throughout the study period in spite of the sPLA2 presence in blood. Incubation of blood serum (6 days post-PTCA) with LDL resulted in accumulation of LPC only for those patients who subsequently developed restenosis. Manoalide, a specific inhibitor of sPLA₂, completely blocked the LPC accumulation. The data indicate that elevated serum sPLA₂ activity after PTCA is associated with restenosis development and may be involved in atherogenic modification of LDL in blood serum. (Mol Cell Biochem 270: 107–113, 2005)