Ca2+-ATPase and function of sarcoplasmic reticulum during cardiac hypertrophy

1991 ◽  
Vol 261 (4) ◽  
pp. L23-L26 ◽  
Author(s):  
Dmitri Levitsky ◽  
Diane De La Bastie ◽  
Ketty Schwartz ◽  
Anne-Marie Lompré
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Calcium Ion ◽  
Adenosine Triphosphatase ◽  
State Level ◽  
Calcium Sensitivity ◽  
Left Ventricular ◽  
Pump System ◽  
Messenger Ribonucleic Acid ◽  
And Function

The properties of the calcium pump system of sarcoplasmic reticulum (SR) were studied in a series of 34 rats subjected to cardiac overload and 19 sham-operated animals. Total homogenates of left ventricle were analyzed by measuring the oxalate-supported Ca2+ uptake rate, the steady-state level of the phosphorylated intermediate of Ca2+-adenosine triphosphatase (Ca2+-ATPase) (E-P), and the amount of Ca2+-ATPase mRNA. All three parameters decreased gradually as a function of the relative left ventricular weight increase. The calcium-sensitivity curves showed that the velocity of Ca2+ transport in SR from the hypertrophied heart is diminished at low as well as optimal Ca2+2 concentrations, with the dissociation constant (Kd) value for Ca2+ unchanged from that of the control preparation. Taken together with the results presented in our recent publication (De la Bastie, Levitsky, Mercadier, Marotte, Wisnewsky, Brovkovivh, Schwartz, and Lompré, Circ. Res. 66: 554–564, 1990), these data strongly indicate that differences in the Ca2+ pump activities of SR from normal and hypertrophied rat hearts are due to quantitative rather than qualitative changes of the Ca2+-ATPase protein. calcium ion uptake; calcium ion adenosine triphosphatase messenger ribonucleic acid; cardiac hypertrophy; monoclonal antibody

Ca2+-ATPase and function of sarcoplasmic reticulum during cardiac hypertrophy

1991 ◽  
Vol 261 (4) ◽  
pp. 23-26 ◽  
Author(s):  
Dmitri Levitsky ◽  
Diane De La Bastie ◽  
Ketty Schwartz ◽  
Anne-Marie Lompré
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Calcium Ion ◽  
Adenosine Triphosphatase ◽  
State Level ◽  
Calcium Sensitivity ◽  
Left Ventricular ◽  
Pump System ◽  
Messenger Ribonucleic Acid ◽  
And Function

The properties of the calcium pump system of sarcoplasmic reticulum (SR) were studied in a series of 34 rats subjected to cardiac overload and 19 sham-operated animals. Total homogenates of left ventricle were analyzed by measuring the oxalate-supported Ca2+ uptake rate, the steady-state level of the phosphorylated intermediate of Ca2+-adenosine triphosphatase (Ca2+-ATPase) (E-P), and the amount of Ca2+-ATPase mRNA. All three parameters decreased gradually as a function of the relative left ventricular weight increase. The calcium-sensitivity curves showed that the velocity of Ca2+ transport in SR from the hypertrophied heart is diminished at low as well as optimal Ca2+ concentrations, with the dissociation constant (Kd) value for Ca2+ unchanged from that of the control preparation. Taken together with the results presented in our recent publication (De la Bastie, Levitsky, Mercadier, Marotte, Wisnewsky, Brovkovivh, Schwartz, and Lompré, Circ. Res. 66: 554–564, 1990), these data strongly indicate that differences in the Ca2+ pump activities of SR from normal and hypertrophied rat hearts are due to quantitative rather than qualitative changes of the Ca2+-ATPase protein. calcium ion uptake; calcium ion adenosine triphosphatase messenger ribonucleic acid; cardiac hypertrophy; monoclonal antibody

Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure overload cardiac hypertrophy

1994 ◽  
Vol 266 (1) ◽  
pp. H68-H78 ◽  
Author(s):  
C. R. Cory ◽  
R. W. Grange ◽  
M. E. Houston
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Atpase Activity ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Tension Development ◽  
Sequestration Potential

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.

Effects of Volatile Anesthetics on Sarcolemmal Calcium Transport and Sarcoplasmic Reticulum Calcium Content in Isolated Myocytes

2002 ◽  
Vol 96 (6) ◽  
pp. 1457-1464 ◽  
Author(s):  
James D. Hannon ◽  
Mark J. Cody
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Adenosine Triphosphatase ◽  
Surface Membrane ◽  
State Level ◽  
Calcium Content ◽  
Right Ventricular Free Wall ◽  
Acetoxymethyl Ester ◽  
Ionic Substitution ◽  
Rate Of Decline ◽  
The Right

Background The surface membrane Ca(2+)-adenosine triphosphatase and Na(+)-Ca(2+) exchanger transport Ca(2+) out of the ventricular myocyte, competing for cytosolic Ca(2+) with the Ca(2+)-adenosine triphosphatase located in the sarcoplasmic reticulum. In this study the authors examined the effects of halothane, isoflurane, and sevoflurane on Ca(2+) extrusion from the cell and sarcoplasmic reticulum Ca(2+) content. Methods Single myocytes from the right ventricular free wall of adult male ferret hearts were isolated, loaded with the acetoxymethyl ester of the fluorescent Ca(2+) indicator fluo-3, and electrically stimulated at 0.25 Hz to reach a steady state level of intracellular Ca(2+) stores. The effects of halothane, isoflurane, and sevoflurane (1 minimum alveolar concentration) on the peak and rate of decline of the Ca(2+) transient induced by 10 mm caffeine were examined. The peak was used as an index of sarcoplasmic reticulum Ca(2+) content, and the rate of decline was used to monitor Ca(2+) extrusion from the cell. Results During control conditions, halothane reduced the Ca(2+) content of the sarcoplasmic reticulum, isoflurane maintained it, and sevoflurane caused it to increase. Halothane did not affect Ca(2+) extrusion from the cell, but both isoflurane and sevoflurane inhibited it. When Na(+)-Ca(2+) exchange was inhibited by ionic substitution, isoflurane and sevoflurane still reduced the rate of Ca(2+) efflux from the cell. However, when the sarcolemmal Ca(2+)-adenosine triphosphatase was inhibited by carboxyeosin, isoflurane and sevoflurane had no effect on Ca(2+) efflux. Conclusions These results suggest that isoflurane and sevoflurane inhibit Ca(2+) transport from the cell via the sarcolemmal Ca(2+)-adenosine triphosphatase. This effect seems to counteract the decrease in Ca(2+) influx through sarcolemmal L-type Ca(2+) channels and maintains sarcoplasmic reticulum Ca(2+) stores.

scholarly journals Primary structure of the calcium ion-transporting adenosine triphosphatase of rabbit skeletal sarcoplasmic reticulum. Soluble peptides from the α-chymotryptic digest of the carboxymethylated protein

1980 ◽  
Vol 187 (3) ◽  
pp. 565-575 ◽  
Author(s):  
G Allen
Keyword(s):  
Amino Acid ◽  
Sarcoplasmic Reticulum ◽  
Primary Structure ◽  
Calcium Ion ◽  
Adenosine Triphosphatase ◽  
British Library ◽  
Tryptic Peptides

The isolation of the soluble peptides from the chymotryptic digest of the calcium-transporting ATPase of rabbit skeletal sarcoplasmic reticulum is described. These peptides were partially sequenced and the information obtained was used to align tryptic peptides of the protein and to confirm sequences within the tryptic peptides. Details of the isolation of some peptides and the amino acid analyses of the peptides are given in Supplementary Publication SUP 50103 (10 pages), which has been deposited with the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.

scholarly journals Loss of Endothelial HIF-Prolyl hydroxylase 2 (PHD2) Induces Cardiac Hypertrophy and Fibrosis

2021 ◽  
Author(s):  
Zhiyu Dai ◽  
Jianding Cheng ◽  
Bin Liu ◽  
Dan Yi ◽  
Anlin Feng ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Adaptive Responses ◽  
Genetic Ablation ◽  
Pathological Cardiac Hypertrophy ◽  
And Function

Cardiac hypertrophy and fibrosis are common adaptive responses to injury and stress, eventually leading to heart failure. Hypoxia signaling is important to the (patho)physiological process of cardiac remodeling. However, the role of endothelial Prolyl-4 hydroxylase 2 (PHD2)/hypoxia inducible factors (HIFs) signaling in the pathogenesis of heart failure remains elusive. We observed a marked decrease of PHD2 expression in heart tissues and cardiovascular endothelial cells from patients with cardiomyopathy. Mice with Tie2-Cre-mediated deletion of Egln1 (encoding PHD2) or tamoxifen-induced endothelial Egln1 deletion exhibited left ventricular hypertrophy and cardiac fibrosis. Genetic ablation and pharmacological inhibition of Hif2a but not Hif1a in endothelial Egln1 deficient mice normalized cardiac size and function. The present studies define for the first time an unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and fibrosis in a HIF-2α dependent manner. Targeting PHD2/HIF-2α signaling may represent a novel therapeutic approach for the treatment of pathological cardiac hypertrophy and failure.

Sub-Antihypertensive Doses of Ramipril Normalize Sarcoplasmic Reticulum Calcium ATPase Expression and Function following Cardiac Hypertrophy in Rats

1998 ◽  
Vol 30 (12) ◽  
pp. 2683-2694 ◽  
Author(s):  
Samuel Y. Boateng ◽  
Anne-Marie L. Seymour ◽  
Nabeela S. Bhutta ◽  
Michael J. Dunn ◽  
Magdi H. Yacoub ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Calcium Atpase ◽  
And Function ◽  
Sarcoplasmic Reticulum Calcium

Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy

1997 ◽  
Vol 272 (1) ◽  
pp. H168-H175 ◽  
Author(s):  
H. Tsutsui ◽  
Y. Ishibashi ◽  
K. Imanaka-Yoshida ◽  
S. Yamamoto ◽  
T. Yoshida ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Protein Level ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Regulatory Proteins ◽  
Control Value ◽  
Abdominal Aortic ◽  
Hypertrophied Myocardium

The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.

Tail-anchored membrane protein SLMAP is a novel regulator of cardiac function at the sarcoplasmic reticulum

2012 ◽  
Vol 302 (5) ◽  
pp. H1138-H1145 ◽  
Author(s):  
Moni Nader ◽  
Bart Westendorp ◽  
Omar Hawari ◽  
Maysoon Salih ◽  
Alexandre F. R. Stewart ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Qt Interval ◽  
Cardiac Electrophysiology ◽  
Transmembrane Domain ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Expression Level ◽  
Subcellular Targeting ◽  
Functional Disturbances ◽  
And Function

Sarcolemmal membrane-associated proteins (SLMAPs) are components of cardiac membranes involved in excitation-contraction (E-C) coupling. Here, we assessed the role of SLMAP in cardiac structure and function. We generated transgenic (Tg) mice with cardiac-restricted overexpression of SLMAP1 bearing the transmembrane domain 2 (TM2) to potentially interfere with endogenous SLMAP through homodimerization and subcellular targeting. Histological examination revealed vacuolated myocardium; the severity of which correlated with the expression level of SLMAP1-TM2. High resolution microscopy showed dilation of the sarcoplasmic reticulum/endoplasmic reticulum (SR/ER) and confocal imaging combined with biochemical analysis indicated targeting of SLMAP1-TM2 to the SR/ER membranes and inappropriate homodimerization. Older (28 wk of age) Tg mice exhibited reduced contractility with impaired relaxation as assessed by left ventricle pressure monitoring. The ventricular dysfunction was associated with electrophysiological abnormalities (elongated QT interval). Younger (5 wk of age) Tg mice also exhibited an elongated QT interval with minimal functional disturbances associated with the activation of the fetal gene program. They were less responsive to isoproterenol challenge (ΔdP/d tmax) and developed electrical and left ventricular pressure alternans. The altered electrophysiological and functional disturbances in Tg mice were associated with diminished expression level of calcium cycling proteins of the sarcoplasmic reticulum such as the ryanodine receptor, Ca2+-ATPase, calsequestrin, and triadin (but not phospholamban), as well as significantly reduced calcium uptake in microsomal fractions. These data demonstrate that SLMAP is a regulator of E-C coupling at the level of the SR and its perturbation results in progressive deterioration of cardiac electrophysiology and function.

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