PINK1 deficiency alters muscle stem cell fate decision and muscle regenerative capacity.

Maintenance of mitochondrial function plays a crucial role in the regulation of muscle stem cell (MuSC), but the underlying mechanisms remain ill defined. In this study, we monitored mitophagy in MuSCS under various myogenic states and examined the role of PINK1 in maintaining regenerative capacity. Results indicate that quiescent MuSCs actively express mitophagy genes and exhibit a measurable mitophagy flux and prominent mitochondrial localization to autophagolysosomes, which become rapidly decreased during activation.

Optic atrophy 1 mediates muscle differentiation by promoting a metabolic switch via the supercomplex assembly factor SCAF1.

Myogenic differentiation is integral for the regeneration of skeletal muscle following tissue damage. Though high-energy post-mitotic muscle relies predominantly on mitochondrial respiration, the importance of mitochondrial remodeling in enabling muscle differentiation and the players involved are not fully known. Here we show that the mitochondrial fusion protein OPA1 is essential for muscle differentiation.

Macrophages Reprogrammed In Vitro Towards the M1 Phenotype and Activated with LPS Extend Lifespan of Mice with Ehrlich Ascites Carcinoma.

BACKGROUND The majority of tumors trigger macrophage reprogramming from an anti-tumor M1 phenotype towards a pro-tumor M2 phenotype. The M2 phenotype promotes tumor growth. We hypothesized that increasing the number of M1 macrophages in a tumor would limit carcinogenesis and extend the lifespan of the tumor host.

[Resistance to acute hypoxia and changes in the phenotype and phenotypic plasticity of macrophages in mice of different genetic strains].

The aim of study was to investigate the effect of hypoxia on the macrophage phenotype and phenotypic plasticity and to determine the resistance to acute hypoxia in C57/BL mice, which have the pro-inflammatory M1 macrophage phenotype, and in BALB/c mice, which have the anti-inflammatory M2 macrophage phenotype. The following results were obtained. 1) The response of macrophages to acute hypoxia has two successive phases, the immediate, anti-inflammatory phase, and the delayed, pro-inflammatory phase.

Adaptation to heat limits stress-induced activation of caspases in the thymus.

We demonstrated selective activation of caspases in the thymus during heat shock, i.e. primary activation of initiator caspase 9 (but not caspase 8) and effector caspase 3 (but not caspase 6).

[Metabolism of catecholamines in children with attention deficit syndrome with hyperactivity].

Unlabelled: The aim of research was to study catecholamine excretion peculiarities of the children with attention deficit hyperactivity disorder (ADHD). 25 children at the age of 7-9 years took part in this research. High-pressure liquid chromatography (HPLC) was used for measuring the content of catecholamine.

Cross-talk between nitric oxide and HSP70 in the antihypotensive effect of adaptation to heat.

In this work, we evaluated the effect of adaptation to heat on the fall of blood pressure (BP) induced by heat shock (HS) and the interrelation between nitric oxide (NO) and heat shock protein, HSP70. Experiments were carried out on Wistar rats. It was shown that HS resulted in a generalized and transient increase in NO production (the electron paramagnetic resonance method) and a fall of BP from 113+/-3 to 88+/-1 mm Hg (p<0.

Is HSP70 involved in nitric oxide-induced protection of the heart?

It is known that HSP70 plays an important role in the antiischaemic effect of adaptation to stress. The aim of our study was to verify the hypothesis that nitric oxide (NO) may contribute to the activation of HSP70 synthesis and to enhance thereby the resistance of organism to the ischaemic and reperfusion damages. We observed that heat shock potentiated NO production in the heart.

[The effect of calmodulin inhibitors and the new cardiotonic drug DPI 201-106 on the formation of interprotein bonds in the cardiac troponin complex].

Using the binding of labeled [125I]troponin C (TnC) to troponin I (TnI) and troponin (TnT) immobilized on a polyvinylchloride matrix, the Ca-dependent formation of interprotein bonds in the cardiac troponin complex and the effects of various drugs on the above reaction were studied. It has been found that in the absence of Ca2+ the dissociation constant, Kd, for the TnC-TnI complex in equal to (2.5 +/- 1.

[Interaction of calcium agonists and antagonists with Ca-binding proteins and their effect on cyclic nucleotide phosphodiesterase].

The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied.

Effect of calmodulin inhibitors on rat and guinea pig myocardial contractility.

The effects of phenothiazine drugs with different affinities for calmodulin (trifluoperazine, frenolone, majeptile and aminazine) on the contractility of rat and guinea pig papillary muscles were studied. The phenothiazine-induced changes in the contraction-relaxation parameters were shown to correlate with the degree of calmodulin inhibition. These parameters are relaxation-onset index, relaxation index and terminal relaxation index in rats, and relaxation index and maximal developed tension in guinea pigs.

[Prevention of adrenaline-induced arrhythmia by a calmodulin blocker, trifluoroperazine].

Adrenergic arrhythmias were induced in isolated rat hearts with epinephrine in a concentration of 5.10(-5) M in the perfusing solution. The rhythm disturbance was accompanied by a pronounced depression of contractility.

[Effect of calcium ions on the interaction of troponin C with rabbit skeletal muscle troponin I and troponin T immobilized on polyvinyl chloride].

Using a new methodological approach based on the binding of 125I-labeled troponin C to troponins I and T immobilized on polyvinylchloride, the Ca2+-dependent interaction of troponin components was investigated. In the absence of Ca2+, two types of sites of troponin C--troponin T interaction were revealed (Kd = 3.6.

[Prevention of ischemic and reperfusion arrhythmias using the calmodulin blocker trifluoperazine].

Models of ischemic and reperfusion arrhythmias were reproduced in isolated rat hearts by means of the ligation and subsequent reocclusion of the left descending coronary artery. The introduction of trifluoperazine (TFP, 10(-6) M) and verapamil (2.5 X 10(-8) M) into the perfusion medium produced a 20% depression of contractility in aerobic conditions; an additional depression of contractility at 20 min of ischemia and 10 min of reperfusion was 40 and 50%, respectively, for TFP and about the same for verapamil, as compared to the control.

[The use of pharmacological preparations for the study of calmodulin interaction with enzymes].

Calmodulin-dependent regulation of cyclic nucleotide phosphodiesterase and kinase phosphorylase activities as well as Ca2+-dependent regulation of kinase phosphorylase, mediated via the integrated calmodulin, were studied in presence of phenothiazine and butyrophenone series of pharmacological drugs. As compared with butyrophenones, phenothiazines were shown to be more effective inhibitors of calmodulin-dependent activation of the phosphodiesterase. Phenothiazines inhibited similarly the effect of calmodulin on activity of kinase phosphorylase, whereas they did not affect the Ca2+-dependent activity of kinase phosphorylase.

[Role of calmodulin in the contractile function of the myocardium].

The effect of phenothiazines-trifluoroperazine frenolone, majeptile and aminazine on contractility of papillar muscle of Wistar male rats associated with short-term Ca-concentration increase up to 4 mM has been studied. There has been found the parameter-relaxation index-the change of which under the effect of phenothiazines (10(-5) M in all the cases) made use of significantly correlates with the constants, which reflect the similarity of given agents with calmodulin.

[Protective effect of aminazine in ischemia and re-perfusion of an isolated heart].

The effect of cholorpromazine on the degree of reduction of the myocardial contractility during reperfusion of the isolated heart after 5 minutes total ischaemia of rats or after 40 minutes ligation of the left coronary artery of the guinea pigs has been studied. It has been shown that in both cases the preparation shows protective effect. In experiments on vesicles of sarcoplasmic reticulum (SR) of rat's skeletal muscles has been established that chlorpromazine prevents from calcium pump of SR dissociation caused by lipid peroxidation activity or by adding phospholipase A2 to SR fragments.

[Calcium-dependent regulation of NAD-isocitrate dehydrogenase in the rat heart mitochondria].

Ions of Ca2+ (0.1-20 mumoles) regulated the activity of mitochondrial NAD-isocitrate dehydrogenase (isocitrate: NAD-oxidoreductase decarboxylating, EC 1.1.

The influence of phenothiazines on the sarcoplasmic reticulum Ca-ATPase from skeletal and cardiac muscles.

Phenothiazines--trifluoperazine, chloropromazine and ethmozine-- inhibit the sarcoplasmic reticulum Ca-ATPase from skeletal and cardiac muscles of the rabbit. The inhibition constants for both preparations are of the same order of magnitude. The experimental data suggest that the effect of phenothiazine on the sarcoplasmic reticulum Ca-ATPase is not mediated by CaM, but is directed toward the enzyme molecule.

[Study of electromechanical coupling in smooth muscle cells of the ureter using phenothiazines].

Chlorpromazine (ClP) and trifluoperazine (TFP) depress electrical and mechanical activity of ureter smooth muscle cells. Contraction was depressed by less doses of the substances applied as compared with the processes responsible for generation of spike activity. ClP causes the displacement of the dose-effect curve for Ca2+ towards larger concentrations of the latter.