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R Vetter

Publications and source records attributed to R Vetter.

70 records · Page 4Linked to original sources

Developmental changes of Ca++ transport systems in chick heart.

Sarcolemma (SL) Na+/Ca++ exchange, binding of the Ca++ channel antagonist [3H]nitrendipine and sarcoplasmic reticulum (SR) Ca++ uptake were studied in crude membranes from developing chick heart. Energy-linked Ca++ uptake of mitochondria (MT) was measured in tissue homogenates. When reckoned per unit of heart mass Na+/Ca++ exchange increases linearly (20-fold) from embryonic day 4 to postnatal day 10. These changes correlate strongly with developmental variations of (Na+, K+)ATPase activity. The density of high-affinity [3H]nitrendipine receptors increases in parallel, while the specific affinity does not change SR Ca++ uptake rises steadily during embryogenesis and increases steeply (3-fold) at the time of hatching. Hearts of 10-day-old chickens exhibit 50-fold higher SR Ca++ transport activities than those of 4-day-old embryos. Between the latter stage and postnatal day 10 a more than 100-fold increase of MT Ca++ uptake occurs. The results suggest developmental variations in the contribution of single Ca++ transporting systems in cardiac Ca++ control.

Age Factors↗

Indirect technique for the estimation of cAMP-dependent and Ca2+/calmodulin-dependent phospholamban phosphorylation state in canine heart in vivo.

An indirect technique was employed to estimate the in vivo phosphorylation state of phospholamban in preparations from dog hearts depleted from catecholamines and from dog hearts treated with isoproterenol. This method allows the separate detection of cAMP-dependent and Ca2+/calmodulin-dependent phospholamban phosphorylation. The data obtained demonstrate the phosphorylation of both the cAMP-dependent and the Ca2+/calmodulin-dependent phosphorylatable site of phospholamban in response to the beta-adrenergic agonist isoproterenol in canine heart in vivo.

Animals↗

Early presence of phospholamban in developing a chick heart.

Phosphorylation of phospholamban and development of reticular Ca2+ transport were studied in crude membrane preparations of embryonic, newborn and adult chick heart. Maximal phosphorylation of phospholamban by added catalytic subunit of cyclic AMP-dependent protein kinase increases from embryonic day 4-15. It decreases with further development. In the same membrane preparations active Ca2+-uptake into vesicles of sarcoplasmic reticulum rises from day 4-7 and decreases then slightly until day 20. A several-fold increase in Ca2+-transport activity occurs at the time of hatching. The data indicate separate genetic control for synthesis of phospholamban and sarcoplasmic reticulum Ca2+-ATPase.

Aging↗

Potentiating effect of calmodulin and catalytic subunit of cyclic AMP-dependent protein kinase on ATP-dependent Ca2+-transport by cardiac sarcolemma.

Highly purified sarcolemmal membranes were prepared from pig heart homogenates by differential and density gradient centrifugations. The membrane fragments exhibit ATP-dependent Ca2+-transport and Na+/Ca2+-exchange activities. ATP-dependent Ca2+-transport (K0.5Ca2+ = 0.3 microM; Vmax = 4.6 nmol Ca2+.mg protein-1.min-1) is not stimulated by oxalate. Ca2+-uptake is also not supported by p-nitro-phenylphosphate. Preincubation of sarcolemma with MgATP, calmodulin and catalytic subunit of cyclic AMP-dependent protein kinase stimulates active Ca2+-transport 1.8-fold. The effects of calmodulin and catalytic subunit are potentiating rather than additive. A large portion of the Ca2+ additionally accumulated after prephosphorylation of membranes is exchangeable for Na+ via the Na+/Ca2+-exchange system.

Adenosine Triphosphate↗

[Diet induced changes of Ca-regulation in rabbit papillary muscle. 1. Contraction and relaxation following a cholesterol diet].

To characterize consequences of cholesterol induced increases of the Na content on the Ca regulation in rabbit myocardium the influence of increasing extracellular Ca (Cae) on isometric contraction and relaxation of papillary muscles has been investigated after a 12 weeks lasting cholesterol-rich diet. After cholesterol-rich diet increasing Cae caused a higher augmentation in peak tension T, accompanied by a decreased index in contractility [Formula: see text], an insignificantly prolonged time to peak tension TPT, and a decrease in the refractory period, which was extended compared with the control group. A delay in relaxation is demonstrated by the maximum relaxation rate [Formula: see text], the half time of relaxation RT 1/2 and more pronounced by a prolonged relaxation time RT. The results correspond with changes in the Na content published earlier and are in agreement with the assumption that a Na-Ca exchange is involved in beat-to-beat regulation in rabbit myocardium; thereby the cholesterol component of atherogenic diet promotes Ca enhancement in rabbit cardiac cells.

Animals↗

[Diet-induced changes on Ca-regulation in rabbit papillary muscle. 2. Contraction, relaxation and rest potentialization following a rapeseed diet].

To characterize consequences of rape oil-induced changes on the Ca regulation in rabbit papillary muscle, the influence of increasing extracellular Ca (Cae) on contraction, relaxation and resting potentiation of tension has been investigated after a 12 weeks lasting rape oil-diet. After oil diet increasing Cae caused a similar augmentation in peak tension T accompanied by an increased index in contractility [Formula: see text], a significantly shortened time to peak tension and a decline in refractory period. A higher relaxation rate is demonstrated by the maximum relaxation rate [Formula: see text], the half time of relaxation RT 1/2 and relaxation time RT. The resting potentiation of the isometric contraction was enhanced. The results are in agreement with the assumption that the sarcoplasmic reticulum (SR) is more involved in Ca regulation after the oil diet than in the control group. This may be related to differences in the phospholipid content of SR membranes.

Animals↗

[Modifications of electromechanical coupling in the rabbit myocardium following cholesterol-oil diet during changing Ca2+ supply].

To characterize the electromechanical coupling in rabbit myocardium after a 12 weeks lasting lipid-rich diet the influence of increasing extracellular Ca2+ on isometric contractions of isolated trabeculae has been investigated. Only after lipid-rich diet the Ca2+-induced augmentation in isometric tension was accompanied by an increase in a Vmax equivalent, in the index of contractility dk/dtmax divided by K', and in the relaxation index -dk/dtmax divided by K. The results correspond with changes in the sarcoplasmic reticulum function reflected in a higher Ca2+ accumulating ability of isolated microsomes.

Animals↗

[Changes in the excitation contraction coupling in the myocardium of rabbits fed a cholesterol-containing diet].

It was of interest whether a hypercholesterolemia after feeding a diet containing 2 g cholesterol in sunflower oil per day during 12 weeks induces changes of the myocardiac cells of rabbits which must not necessarily be the consequence of a diminished bloodstream on account of coronary stenosis or the consequence of a lesion of the wall of the vessels. The contractile force and the indirectly measured shortening velocity of the isometrically working papillary muscle out of the left ventricle were not reliably changed. As a result of the feeding the isometric force rose after paired pulse stimulation and after a pause during the rhythmic action, although a considerable deposition of fat within the cells and disseminated necrosis in the myocardium could be observed. Because of the increasing loss of sodium into sodium-free solution in parallel with an increasing sodium content of the myocardium it has been concluded that the permeability of the cell membrane for this ion should be elevated. Furthermore it is assumed that the activation of the ionic pumps is elevated which is recognizable from a higher positive inotropic action of both the application of strophanthine and the substitution of NaCl by LiCl. But it seems that one elevation could not completely compensate the other one. The mean value of the velocity of relaxation related to the isometric force was increased. It has been postulated that after the diet rich in cholesterol and sunflower oil the cardiac cell shows a retarded restitution of the contraction during the interval between beats and elevated content of calcium. This may be one of the causes for the observed necrosis besides the ischemic component of the injurant feeding.

Animals↗

Interactions between cyclic AMP-dependent protein phosphorylation and lipid transmethylation reactions in isolated porcine cardiac sarcolemma.

Premethylation of purified porcine cardiac sarcolemma (SL) in the presence of 0.15, 10 and 150 microM S-adenosyl-L-methionine (AdoMet) did not change the phosphorylation of SL proteins catalyzed either by intrinsic cyclic AMP-dependent protein kinase (cAK) or by added catalytic (C) subunit of this enzyme. On the other hand, membrane exhibited increased lipid methyltransferase activity after preincubation with MgATP and C subunit. Prephosphorylation of membranes stimulated the total [3H]-methyl incorporation into SL lipids assayed at 0.15 microM [3H]AdoMet due to an enhancement of Vmax and without changes in the Km value for AdoMet. Analysis of the methylated lipid products revealed an increased methyl group incorporation into a nonpolar lipid fraction whereas phosphatidylethanolamine-N-methylation was not affected by phosphorylation. The results suggest that the cyclic AMP-mediated signal transduction at the level of cardiac SL is not affected by methylation-induced modifications of the membrane lipid microdomains. On the other hand, an intrinsic SL lipid methyltransferase activity is apparently not related to the N-methylation of phospholipids, is modulated by cyclic AMP-dependent protein phosphorylation.

Adenosine Triphosphate↗

Early postnatal changes in sarcoplasmic reticulum calcium transport function in spontaneously hypertensive rats.

This comparative study investigates the relationship between sarcoplasmic reticulum (SR) calcium(Ca2+)-ATPase transport activity and phospholamban (PLB) phosphorylation in whole cardiac homogenates of spontaneously hypertensive rats (SHR) and their parent, normotensive Wistar Kyoto (WKY) strain during early postnatal development at days 1, 3, 6, 12 and at day 40 to ascertain any difference in SR Ca2+ handling before the onset of hypertension. At day 1, the rate of homogenate oxalate-supported Ca2+ uptake was significantly higher in SHR than in WKY (0.25 +/- 0.02 vs 0.12 +/- 0.01 nmoles Ca2+/mg wet ventricular weight/min, respectively; p < 0.001). This interstrain difference disappeared with further developmental increase in SR Ca2+ transport. Western Blot analysis and a semiquantitative ELISA did not reveal any difference in the amount of immunoreactive PLB (per mg of total tissue protein) between strains at any of the ages studied. In addition, levels of phosphorylated PLB formed in vitro in the presence of radiolabelled ATP and catalytic (C) subunit of protein kinase A did not differ between SHR and WKY at days 1, 3, 6 and 12. At day 40, C subunit-catalyzed formation of 32P-PLB was reduced by 66% (p < 0.001) in SHR when compared to age-matched WKY. In the early postnatal period between day 1 and 12 SR Ca(2+)-transport values were linearly related to the respective 32P-PLB levels of both SHR and WKY rats. The results indicate that cardiac SR of SHR can sequester Ca2+ at a much higher rate immediately after birth compared to WKY rats. The disappearance of this interstrain difference with further development suggests that some endogenous neuroendocrine or nutritional factor(s) from the hypertensive mother may exert an influence upon the developing heart in utero resulting in a transiently advanced maturation of the SR Ca2+ transport function in SHR pups at the time of birth.

Animals↗

Subband modeling of the human cardiovascular system: new insights into cardiovascular regulation.

We present a new approach to cardiovascular analysis based on a well-known signal processing technique, namely, the frequency subband decomposition. The subbands are chosen in accordance with physiological standards: (1) 0-0.04 Hz, (2) 0.04-0.15 Hz, (3) 0.15-0.4 Hz. It is shown that such a pre-processing drastically improves the accuracy of the analysis and introduces a new direction in the understanding of the relationships between cardiovascular signals.

Adult↗

The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1 and HLA-DR expression on hyperproliferative keratinocytes. Quantification by a culture plate-directed APAAP-ELISA technique.

The derivatives of fumaric acid show antipsoriatic effects but details of the mechanism of action are largely unknown. The study focused on the effect of fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its derivatives for 48 hrs. The effect of fumarates was investigated semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP-ELISA technique. The semiquantitative evaluation revealed that in the micromolar dose range investigated only dimethyl-fumarate demonstrated substantial growth inhibition and down-regulation of the cell surface markers. In the quantitative evaluation, dimethyl-fumarate significantly (p</=0.05) suppressed the expression of ICAM-1 (84%) and HLA-DR (67%) on HaCaT keratinocytes at a subtoxic concentration of 4.0 microM as compared to untreated controls (100%). In contrast, concentrations of 4.0, 12 and 35 microM dimethyl-fumarate had no influence on the ICAM-1 and HLA-DR expression on IFN-gamma-exposed normal human epidermal keratinocytes in primary cultures. Thus, there is experimental evidence that dimethyl-fumarate may exert its antipsoriatic effect not only as an antiproliferative agent but also by down-regulation of ICAM-1 and HLA-DR molecules on hyperproliferative keratinocytes.

Cell Division↗