The mutation Arg91Gly (R91G) in beta-tropomyosin (beta-TM) is known to cause distal arthrogryposis, a severe congenital disorder of muscle tissues. To elucidate how this mutation affects the structural properties of beta-TM, the thermal unfolding of beta-TM carrying mutation Arg91Gly was compared with that of the wild type protein. It was shown by differential scanning calorimetry and circular dichroism that this point mutation dramatically decreases the thermal stability of a significant part of beta-TM (about a half of the molecule).
View Article and Find Full Text PDFWe applied different methods to analyze the effects of the recombinant wild-type small heat shock protein with an apparent molecular mass of 27 kD (Hsp27-wt) and its S15,78,82D mutant (Hsp27-3D), which mimics the naturally occurring phosphorylation of this protein, on the thermal denaturation and aggregation of F-actin. It has been shown that, at the weight ratio of Hsp27/actin equal to 1/4, both Hsp27-wt and Hsp27-3D do not affect the thermal unfolding of F-actin but effectively prevent the aggregation of F-actin by forming soluble complexes with denatured actin. The formation of these complexes occurs upon heating and accompanies the F-actin thermal denaturation.
View Article and Find Full Text PDFThis short review is concerned with the application of the method of differential scanning calorimetry to study the conformational changes of isolated myosin head (myosin subfragment 1, S1) caused by the formation of the S1 complexes with Mg(2+)-ADP and P(i) analogues such as orthovanadate (V), aluminium fluoride (AIF4-) or beryllium fluoride (BeFx). These changes of the whole S1 molecule are reflected in a significant increase of S1 thermal stability and in a pronounced increase of the cooperativity of the thermal denaturation. Since the complexes S1-ADP-V, S1-ADP-AIF4- and S1-ADP-BeFx are stable analogues of the S1**-ADP-P(i) transition state of the S1-catalyzed ATP hydrolysis, it is concluded that DSC studies with these complexes offer a new and promising approach to investigate the structural changes which occur in the myosin head during Mg(2+)-ATPase reaction.
View Article and Find Full Text PDFThe effects of trinitrophenylation of lysyl residues of rabbit skeletal myosin subfragment 1 (S1) on thermal denaturation of S1 in the absence of nucleotides, in the presence of ADP and within S1 complexes with ADP and Pi analogues, orthovanadate (Vi) or beryllium fluoride (BeFx), have been studied by differential scanning calorimetry. It has been shown that lysyl trinitrophenylation significantly affects the thermal stability of S1, changes its domain structure, promotes the decomposition of S1.ADP.
View Article and Find Full Text PDFEchinochrom, a new antioxidant of the polyhydroxynaphthaquinone class, was tested for its cardioprotective activity in a model of occlusive reperfusion myocardial infarction (90-min occlusion and 4-hour reperfusion) in the acute experiments with open-chest dogs. The bolus intravenous injection of echinochrom in a dose of 1 mg/kg 5 min before reperfusion caused a significant (over 40%) reduction in the size of a necrotic focus. A supplementary administration of echinochrom 5 min after the onset of ischemia failed to contribute to a significant enhancement of its protective effect, suggesting that there is no substantial effect of the agent on ischemic lesion.
View Article and Find Full Text PDFThe current data and concepts of the structural organization of the head of myosin, one of the major muscle proteins, are reviewed. The primary structure of the isolated myosin head (myosin subfragment-1) heavy chain and localization in it of sites and groups responsible for the binding and hydrolysis of ATP and myosin interaction with actin, are considered. Evidence is given of reciprocal spatial distribution of these sites and their localization on the myosin head surface.
View Article and Find Full Text PDFThe clinical effects of Tenoric, a long-acting combined drug (atenolol and chlorthalidone in a tablet), were studied in 31 patients with Stages I and II hypertensive disease, by using echocardiography, daily automatic blood pressure monitoring, bicycle ergometry, measurements of plasma renin and aldosterone. The drug was found to be highly clinically effective in labile and sustained hypertension. When given once or twice a day, it makes it possible to reliably monitor blood pressure, improve hemodynamic parameters, as reflected by lower cardiac output and decreased peripheral vascular resistance, reduce the estimated mass of the left myocardium, alleviate a pressor response to exercise and enhance its tolerance, lower plasma renin levels.
View Article and Find Full Text PDFUsing polarization microfluorimetry, the interaction of myosin subfragment 1 (S1) isoforms containing alkali light chains A1 and A2 respectively (S1(A1) and S1(A2] with F-actin of single glycerinated rabbit skeletal muscle fibers was studied. The alkali light chains of S1 were substituted by reassociation for A1 or A2 chains modified by a fluorescent label (1.5-IAEDANS) at the single SH-group located in the C-terminus.
View Article and Find Full Text PDFAn experimental mathematical model was proposed to assess the efficiency of experimental myocardial infarction (MI) size limitation. A canine model of occlusion-reperfusion myocardial lesion was used in an acute experiment with an open chest. 90-minute occlusion and 4-hour reperfusion were performed by carotid coronary bypass surgery.
View Article and Find Full Text PDFThermal denaturation of myosin rod has been studied by differential scanning microcalorimetry and intrinsic tryptophane fluorescence methods. Use of the sequence annealing in the calorimetric measurement allows to decompose the total thermogram of rod into four elementary bands with maxima at 42, 46.5, 50 and 57 degrees C.
View Article and Find Full Text PDFPlanar bilayer lipid membranes formed from trepang phospholipids possess an intrinsic Ca2(+)-permeability. These phospholipids dissolved in a non-polar solvent can extract 45Ca2+ from the aqueous to the organic phase. The triterpenic glycoside holotoxin A isolated from the trepang Stichopus japonicus inhibits the Ca2+ flux of lipid bilayers from trepang phospholipids as well as the Ca2+ flux induced in phosphatidylcholine bilayers by the calcium ionophore X-537A.
View Article and Find Full Text PDFA study was made of the relationship between Na-Li countertransport and arterial blood pressure in 95 persons selected at random from the representative sample (n = 1716) of the population of one of the districts of Moscow. Of these, 34 persons turned out to be normotensive, 15 had borderline hypertension, 44 stable essential hypertension, and 2 persons presented with secondary hypertension. A positive correlation was found between countertransport and age and weight, determining 20.
View Article and Find Full Text PDFThe rate of Na-Li countertransport was studied in inpatients with essential hypertension (n = 59), chronic diffuse glomerulonephritis (n = 30), chronic pyelonephritis (n = 26), renovascular hypertension (n = 15) and in those with associated renovascular hypertension and essential hypertension (n = 4). Multiple regression analysis has demonstrated that age, body weight and blood plasma lipids do not make any significant contribution to dispersion of the counter transport rate. The mean rate of countertransport in patients with essential hypertension turned out much higher than that in patients with secondary hypertensions.
View Article and Find Full Text PDFSodium ion interaction with sarcoplasmic reticulum (SR) membranes leads to considerable alterations of the [23Na]NMR lineshape. Na+ binding to SR in the presence of Ca2+ and H+ is well described by a model which postulates a competitive ion binding to high and low affinity sites of Ca2+-ATPase. The dissociation constant, Kd, for high and low affinity sites is 5 and 10 mM, respectively, for Na+ and (3-5).
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